Parkinson's disease (paralysis agitans, PD)
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Introduction
In 1817 James Parkinson, a London physician, described the motor disorder that now bears his name:
'... involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported, with a propensity to bend the trunk forwards, and to pass from a walking to a running pace, the senses and intellects being uninjured.'
Etiology
- idiopathic
- viral encephalitis (rare)
- focal lesions of the substantia nigra (rare)
- Parkinson's disease may occur as a result of single event rather than a chronic process:
- progressive neurodegeneration after exposure to a neurotoxin earlier in life
- delayed onset of parkinsonism after encephalitis lethargica
- traumatic brain injury in older adults increases risk of Parkinson's disease[80]
- parasopmnias including REM sleep behavior disorder may play a role [115. 172]
- risk factors include:
- alcohol misuse (RR=1.32)[172]
- hypertension (RR=1.29)[172]
- anosmia, primarily white men (RR=2.16)[103][172] & sensory impairments beyond anosmia
- restless legs syndrome (RR=4.19)*[172]
- tremor (RR=4.49)*[172]
- sleep apnea (RR=1.45)[172]
- epilepsy (RR=2.26)[172]
- migraine (RR=1.21)[172]
- bipolar disorder (RR=3.81)*[172]
- schizophrenia (RR=4.48)*[172]
- skin disorders
- gastrointestinal disorders
- gastroesophageal reflux (RR=1.29)[172]
- gastritis (RR=1.28)[172]
- ulcerative colitis, 0.37 vs 0.22 per 1000 person-years[112]
- gastroparesis, dysphagia, constipation: > 2-fold risk within 5 years[180]
- nearly all patients with Parkinson's disease experience digestive problems & lesions in intrinsic & extrinsic innervation of the GI tract[187]
- seronegative osteoarthritis (RR=1.21)[172]
- diabetes mellitus type-1 (RR=1.32)[172]
- diabetes mellitus type-2 (RR=1.24-1.3)[114][172]
- pesticides
- air pollution: nitrogen dioxide (NO2)[148]
- welding
- volatile organic compounds[178]
- copper ?[161]
- milk (men)[21][28]
- oophorectomy before menopause (RR 1.8)[32]
- statin use may increase risk (RR=1.6-1.7)[92]
- lower HDL cholesterol & increased HDL cholesterol variability may increase risk[146]
- statin use associated with worse baseline nigrostriatal dopamine degeneration[152]
- statin use prior to diagnosis associated with increased risk of dementia[152]
- anticonvulsants including lamotrigine, levetiracetam, & sodium valproate with weaker evidence for carbamazepine may increase risk of Parkinson's disease (RR ~1.8)[171]
- depression ?[81]
- intestinal flora may play a role[113]
- decrease in Lactococcus, Streptococcus, & Lactobacillus
- lytic bacteriophages in the fecal microbiome may play a role in regulation of intestinal flora[113]
* symptoms may be present 5-10 years prior to diagnosis of Parkinson's disease[172]
* reduced risk associated with:
- coffee & caffeine consumption[8]
- higher serum uric acid[22]
* calcium channel blockers[33]
* truncal vagotomy may decrease risk of PD[95]
* beta-2 adrenergic receptor agonists may reduce expression of alpha-synuclein & risk of Parkinson's disease[101]
* increased physical activity (RR=0.79)[118][135]
* high serum cholesterol & LDL cholesterol has a protective effect[92][97] (RR ~0.9 cited)
* maybe vitamin E & vitamin C[147]
* maybe vitamin B12[176]
- not folate of vitamin B6[176]
Epidemiology
- Incidence: 13-20 cases/100,000
- incidence rate ~90,000 cases annually for people >= 65 years[169]
- Prevalence: 187 cases/100,000[15][42]
- lifetime risk 1-2%[15]
- usual age of onset: 50-70 years; can occur after age 20
- more common in males, M:F ratio 3:2[15]
- rare familial forms with autosomal dominant inheritance
- increased incidence in rural areas, drinking well water
- a cluster of counties with higher Parkinson's incidence in Midwestern & Southern regions of the country[169]
- incidence also were elevated in southern California, southeastern Texas, central Pennsylvania, and Florida[169]
- between 1975 & 1985, water supplies at Camp Lejeune were contaminated with several volatile organic compounds[178]
- levels were highest for trichloroethylene, with median values > 70-fold permissible levels[178]
Pathology
- selective neuronal loss
- pars compacta of substantia nigra (dopaminergic neurons)
- neuronal loss greatest in ventrolateral tier, followed by medial ventral tier & dorsal tier
- 60-70% loss at onset of symptoms
- pattern of neuronal loss opposite that in normal aging
- loss of striatal dopaminergic projections most prominent in dorsal & intermediate subdivisions of putamen
- deficit in dopamine release
- down-regulation of dopamine transporters in part compensates for loss of dopaminergic terminals[36]
- cholinergic hypersensitivity within the striatum[15]
- results in excessive inhibitory output of the globus pallidus interna to the thalamus[15]
- retinal thinning may be linked to dopaminergic neuronal atrophy[117]
- locus ceruleus
- deficit in norepinephrine release
- raphe nuclei
- hypothalamic neurons
- small cortical neurons
- nucleus basalis of Meynert
- olfactory bulb
- sympathetic ganglia
- parasympathetic neurons in gut
- projection cells that generate long, unmyelinated or sparsely myelinated axons[29]
- peripheral autonomic nerves may be affected before the brainstem[115]
- serotonergic pathology in premotor A53T SNCA carriers may precede development of dopaminergic pathology & motor symptoms[132]
- pars compacta of substantia nigra (dopaminergic neurons)
- Lewy bodies
- Lewy neurites
- degenerating neurites containing
- ubiquitin
- alpha-synuclein
- copper modifies & accelerates alpha synuclein aggregation[161]
- found in affected brainstem regions
- especially prominent in dorsal nucleus of vagus
- cognitive impairment correlates with Lewy neurites in CA2 region of hippocampus
- degenerating neurites containing
- diminished glucocerebrosidase activity appears to be an early step in degeneration of dopaminergic neurons[94]
- possible preventive effect of truncal vagotomy on incidence of PD provides support for Braak hypothesis that PD begins in the gut & spreads to the brain[95]
- early caudate dysfunction may increase risk for later cognitive impairment & depression[128]
- alterations in gut microbiome
- alterations in intestinal permeability[113]
- Lactococcus & Lactobacillus regulate intestinal permeability & are diminished in intestinal flora of PD patients[113]
- lytic bacteriophages may play a role in diminished intestinal Lactococcus[113]
- vermiform appendix may play a role[121]
- 46 of 48 healthy human appendixes with insoluble alpha-synuclein, similar to alpha-synuclein found in brains of patients with Parkinson's disease[121]
- appendectomy lowers risk of Parkinson's disease[121]
- reduced abundance Roseburia faecis, Eubacterium rectale, and E. ramulus (known for flavonoid degradation), Oscillibacter_sp_57_20, Bacteroides xylanisolvens, E. siraeum[184]
- increased abundance of Bifidobacterium dentium, B. longum, E. tayi, C. leptum, R. lactatiformans[184]
- reduced retinal ganglion cell-inner plexiform layer thickness & reduced retinal inner nuclear layer thickness as determined by optical coherence tomography[179]
Genetics
- autosomal dominant forms[31]
- alpha-synuclein gene (SNCA) mutations
- UCH-L1 mutations (ubiquitin carboxyl-terminal hydrolase)
- chromosome 2q
- LRRK2 (along with parkin, most common genetic form)
- p.G2019S
- autosomal recessive
- parkin (PARK2) (no Lewy bodies)
- DJ-1
- PINK1
- up-regulation of DDIT4, CPLX1 in substantia nigra neurons
- twin studies:
- if < 55 years of age, relative risk = 6.0
- if > 55 years of age, no increased risk
- variants in the GBA1 gene are associated with faster disease progression[183]
- other implicated genes:
- associated with cholinergic & monoaminergic neurons (including dopaminergic neurons) & with enteric neurons & oligodendrocytes[140]
- > 2000 specific bacteriophages infecting gut bacteria are associated human chronic diseases, particularly Parkinson disease & obesity[149]
- many of the viral sequences are integrated into human chromosomal DNA or in circular episomes[149]
History
- review diagnosis, psychiatric symptoms, autonomic symptoms
- ask about cognitive impairment, sleep disturbance, adverse drug effects[91]
Clinical manifestations
- onset: between ages 40 & 70
- preclinical symptoms[24][76][131][170]
- tremor within 2 years of diagnosis (41%)[76]
- within 2-5 years of diagnosis
- tremor, constipation, balance problems, hypotension, erectile dysfunction, urinary dysfunction, dizziness, fatigue, depression, anxiety[76]
- within 5-10 years of diagnosis
- 3 years prior to diagnosis
- problems with walking, balance, lifting heavy objects[170]
- other
- anosmia (loss of smell)
- slow reaction time
- excessive daytime sleepiness
- REM sleep behavior disorder[131][135] (wild dreams)
- impaired color vision[135]
- anosmia, constipation, REM sleep behavior disorder may precede movement disorder in a subgroup of patients[3]
- depression may precede movement disorder in a subgroup of patients[70][81]
- presenting symptoms:
- classic triad of: tremor, rigidity, bradykinesia*
- cerebellar signs normal: finger-to-nose & heel-to-shin intact[6]
- postural reflex abnormality (falling)*
- shuffling gait & changes in posture
- loss of dexterity, deterioration of handwriting, difficulties in getting up from a chair or out of bed,
- asymmetry of symptoms at presentation, often with persistence of asymmetry[6]
- leg motor restlessness
- tremor at rest* (4-5 Hz)[111]
- first noted in the hands & fingers "pin rolling"
- later may involve legs, face & tongue
- may be unilateral at the onset (asymmetry is the rule)
- exacerbated by anxiety
- absent during sleep
- a faster (7-8 Hz) "action tremor" may be present
- superimposition of tremor on passive movements creates a sense of "cogwheel rigidity" best demonstrated at the wrist
- postural abnormalities:
- flexion of the head, trunk, elbows, & knees, & positional deformities of the hands
- postural tremor[110]
- infrequent eye blinking
- a fixed, expressionless "masked" face
- decreased arm movements while walking
- bradykinesia*
- frequent falls may occur, but are generally a late feature
- backward falls
- pull test predicts likelihood of backward falls
- early falls suggests parkinson plus syndrome
- additional signs may include:
- autonomic dysfunction:
- orthostatic hypotension (advanced disease)
- constipation, diarrhea
- urinary frequency, urinary urgency
- hyperhidrosis (excessive sweating)
- sialorrhea (diminished swallowing of saliva)
- dyspnea (shortness of breath)
- seborrhea
- hyposmia
- sensory symptoms
- micrographia
- dysarthria & hypophonia
- dysphagia
- choking or coughing with eating
- regurgitation is uncommon[16]
- hypometric saccades
- seborrhea
- subtle dementia (25-30%) (see Parkinson's dementia)
- rarely the presenting symptom; tends to occur late[15]
- generally reflects subcortical pattern
- cognitive dysfunction can be a prodromal sign[108]
- depression#[21], anxiety, apathy[6]
- excessive daytime sleepiness# (51%)[12]
- autonomic dysfunction:
- tendon reflexes & sensory pathways are normal
- any of the signs/symptoms may occur alone making the diagnosis of Parkinson's disease difficult without the passage of time & progession of signs/symptoms
- early falls, rapid progression, poor response to Sinemet, dementia, early autonomic failure, cerebellar ataxia suggest other disorders (see differential diagnosis & parkinsonism)[6]
* major criteria for diagnosis, bradykinesia + at least one other[6] (see diagnostic criteria for Parkinson's disease)
# not L-dopa/carbidopa responsive[15]
Diagnostic criteria
- bradykinesia
- at least one other feature of Parkinson's disease
- resting tremor
- cogwheel rigidity
- gait disorder or balance disorder
- absence of sign/symptoms of parkinson plus syndrome
Laboratory
- CSF typically normal
- alpha synuclein aggregates in CSF
- neuronally derived extracellular vesicle alpha-synuclein Ag in serum
- specificity for alpha-synucleinopathy of 80% within 12 years[189]
- higher levels of neurofilament light chain in serum in multiple system atrophy or progressive supranuclear palsy than in Parkinson's disease & healthy controls
- L-dopa decarboxylase in CSF[185]
- HDL cholesterol in serum
Diagnostic procedures
- EEG typically normal
- polysomnography may be useful in the treatment of a comorbid sleep disorder[50]
- ophthalmoscopy & retinal optical coherence tomography for retinal thinning* may suggest early cognitive changes in Parkinson's disease[117][144][179]
* reduced retinal ganglion cell-inner plexiform layer thickness & reduced retinal inner nuclear layer thickness may be seen by optical coherence tomography years before diagnosis of Parkinson's disease[179]
Radiology
- neuroimaging (CT &/or MRI) typically normal
- neuroimaging not routinely required for diagnosis[6][85]
- utility is to exclude other diagnoses[6]
- MRI for exclusionary criteria[15]
- NO lacunar infarcts, normal pressure hydrocephalus, cerebellar atrophy, brainstem atrophy
- pixel-based analysis of MRI neuroimaging to analyze micro- & macro- structural changes in white-matter tracts may identify PD patients with visual hallucination, visual dysfunction or both[137]
- SPECT* of brain reserved for differentiating Parkinson's disease from drug-induced parkinsonism & in difficult cases of essential tremor[6]
- [11]C-DASB PET scan to assess serotonergic neurotransmitter system prior to diagnosis of Parkinson's disease (investigational)
* detects dopamine transporter (DAT scan)[6]
Complications
- oropharyngeal dysphagia[71]
- aspiration pneumonia
- dysphagia for medications is common (67-70%)[168]
- decubitus ulcers & other problems associated with inanition occur in advanced cases
- hallucinations
- dopamine agonists & cognitive impairment contribute
- serotonin 2A receptors may be involved[40]
- visual hallucinations & visual-processing abnormalities may be harbingers of Parkinson's dementia[137]
- excessive sleep & sleep attacks may be associated with dopaminergic agonists[13][20]
- disordered sleep (85%)[16]
- sleep fragmentation most common
- diminished slow-wave sleep may be associated with loss of working memory[50]
- rapid eye movement sleep behavioral disorder
- periodic limb movements
- nocturnal myoclonus
- nocturnal immobility
- sleep-related respiratory dysrhythmias
- nocturnal psychiatric disturbance
- oxygen-desaturation may be associated with loss of working memory[50]
- NOT responsive to L-dopa[15]
- other sleep-related disorders[6]
- restless legs syndrome
- sleep-wake reversal
- distressing dreams are associated with faster cognitive decline & increased risk of dementia[166]
- autonomic disorders[6]
- postural hypotension
- common, RR=3.at baseline & 5 at 7 years
- prevalence: 64% with 29% clinically significant
- cognition worsens when sitting or standing in PD patients with orthostatic hypotension[93]
- common, RR=3.at baseline & 5 at 7 years
- urinary incontinence
- sexual dysfunction
- constipation
- sialorrhea
- seborrhea
- excessive sweating
- postural hypotension
- falls may result in fracture or subdural hematoma
- increased risk of melanoma (HR = 2.2)[39]
- behavioral disorders[6]
- cognitive impairment[6]
- bradyphrenia, confusion, Parkinson's dementia
- may be an early sign of impending parkinsonism & Parkinson's disease[108]
- depression, anxiety, apathy[6][71]
- apathy disrupts white-matter networks & executive function[141]
- delusions, psychosis[6]
- musculoskeletal[6]
- truncal & neck flexion
- dystonic joint deformities: flexion of metacarpal joints, extension of proximal interphalangeal joints[6]
- frozen shoulder[6]
- osteoarthritis 153]
- pain-related[6]
- painful dystonia, painful rigidity
- visceral painful sensations
- primary central pain
- neuroleptic malignant syndrome caused by withdrawal of dopaminergic agent, carbodopa/levodopa or dopaminergic receptor agonist[6]
- weight loss in Parkinson's disease is associated with dementia, dependency & mortality[106]
- frailty is common leading to increased morbidity & mortality[153]
* impulse control disorder may be drug-related[6]
- disease interaction(s) of diabetes mellitus with Parkinson's disease.
- disease interaction(s) of prediabetes with Parkinson's disease.
- disease interaction(s) of osteoarthritis with Parkinson's disease
- disease interaction(s) of Parkinson's disease with depression
- disease interaction(s) of with urinary incontinence
- disease interaction(s) of Parkinson's disease with urinary incontinence
Differential diagnosis
- depression
- essential tremor
- Parkinson plus syndromes
- progressive supranuclear palsy
- multiple system atrophy
- olivopontocerebellar degeneration
- inability to move eyes vertically
- Shy Drager syndrome
- nigrostiatal degeneration
- olivopontocerebellar degeneration
- diffuse Lewy body disease (LBD)
- early dementia within 1st year of parkinsonism suggests LBD[6]
- hallucination plus REM-sleep disorder suggests LBD[26]
- secondary parkinsonism
- head trauma (professional boxing)
- metabolic disorders - hypoparathyroidism
- cerebrovascular disease[15]
- normal pressure hydrocephalus[15]
- post-viral encephalitis
- toxins
- pharmacologic agents produce symmetric motor effects*
- cerebrovascular disease (CVD)
- CVD also with shuffling gait & retropulsion
- multistep turning & increased muscle tone of CVD maybe confused with PD
- tremor, cogwheel rigidity & festination of PD absent in CVD
* absence of a response to high-dose L-dopa/carbidopa is the strongest predictor of an atypical parkinsonism syndrome[6]
* early symmetric signs/symptoms, early falls, early autonomic disorder, early dementia, rapid progression, cerebellar signs (ataxia) or poor response to Simemet suggest other diagnosis[6]
* gaze palsy (PSP), recent neuroleptic use suggest other diagnosis[6]
* non-motor features of Parkinson's disease are not elicited by pharmaceuticals[6]
Management
- drug-induced parkinsonism is treated by stopping or diminishing the dose of offending drug
- pharmaceutical treatment of symptoms when disability becomes apparent, i.e. when symtoms begin to interfere with function[6]
- suppression of resting tremor in mild cases
- anticholinergics (trihexyphenidyl or benztropine)
- antagonize striatal cholinergic hypersensitivity
- anticholinergics associated with worsened cognitive function in Parkinson patients[41]
- trihexyphenidyl, benztropine, biperiden[6]
- amantadine (Symmetrel)
- more useful late in the disease
- treatment of Sinemet induced dyskinesias
- primidone may also be of value
- anticholinergics (trihexyphenidyl or benztropine)
- Sinemet (carbidopa/levodopa)
- first line drug for initial therapy for elderly[6][72]
- 7 years outcomes better & adverse effects & discontinuation rates lower relative to initiation of therapy with MAO-B inhibitor or dopamine agonist[72]
- mainstay of therapy in elderly & in most other cases
- TID or more frequent dosing to minimize motor fluctuations
- combinations of sustained-release TID & regular every 3-4 hours
- therapeutic window narrows with more advanced disease
- amantadine (Gocovri) for treatment of Sinemet-induced dyskinesias[99]
- for levodopa-induced orthostasis (new onset orthostasis with Sinemet therapy) increase dose of carbidopa[11] (also see orthostatic hypotension)[6]
- continuous delivery of levodopa-carbidopa with an intestinal gel delivered through a percutaneous gastrojenunal tube may be of benefit for patients with advanced Parkinson's disease[62]
- early Sinemet neither neuroprotective nor harmful[124]
- quality of life among PD patients with motor complications uncontrolled by levodopa superior when MAO-B inhibitors or dopamine agonists were used as adjuvant treatment compared with COMT inhibitors[159]
- foscarbidopa/foslevodopa by continuous subcutaneous infusion (investigational)
- first line drug for initial therapy for elderly[6][72]
- dopamine receptor agonists
- 1st line for patients < 65 years of age[6]
- useful in patients < 50 years of age[15]
- used to delay the need for Sinemet (MKSAP19)[6]
- replace with Sinemet if adverse effects (hallucinations, worsening motor function) become problematic[124][142]
- not useful in treating early stages to delay the need for Sinemet[34]
- may have neuroprotective effects[10][15]
- less likely than Sinemet to cause extrapyramidal effects
- agents
- bromocryptine
- pergolide
- amantadine
- pramipexole (Mirapex)
- ropinirole (Requip)
- rotigotine (Neupro) patch
- apomorphine
- parenteral
- sublingual form may be useful for off episodes[136]
- cabergoline
- lisuride
- piribedil
- associated with impulse control disorders[116]
- avoid dopamine receptor antagonists[91]
- 1st line for patients < 65 years of age[6]
- MAO inhibitors
- L-deprenyl (Selegiline)
- appears not to slow disease progression[15]
- the combination of L-deprenyl & Sinemet may produce an undesired outcome
- rasagiline
- safinamide (Xadago) FDA-approved for treatment of "off" episodes with levodopa/carbidopa
- MAO-B inhibitors may be underused as adjuvant therapy to levodopa[159]
- L-deprenyl (Selegiline)
- COMT* inhibitors inhibit L-dopa catabolism
- dopaminergic therapy may increase creativity in patients with Parkinson's disease
- potential therapies
- adding carbidopa to Sinemet + entacapone may reduce "off" time[125]
- 105 mg carbidopa vs 65 mg with 75, 100, 125, or 150 mg of levodopa + 200 mg of entacapone
- exenatide may have symptomatic benefit[100]
- anticonvulsants - zonisamide may be of benefit[30]
- anticonvulsants associated with diminishes quality of life[151]
- CoQ10 300-1200 mg/day; 100 mg/day might slow progression of Parkinson's disease[15][17]
- rivastigmine may improve gait stability & reduce risk of falls (RR=0.58)[87]
- prasinezumab, a monoclonal antibody targeting alpha-synuclein aggregates of no benefit for early Parkinson's disease[163]
- venglustat of no benefit in GBA1-associated Parkinson's disease[183]
- gene therapy[60][127]
- other investigational treatments
- see investigational treatment of Parkinson's disease
- adding carbidopa to Sinemet + entacapone may reduce "off" time[125]
- hallucinations/psychosis[61]
- clozapine is effective for controlling psychosis & hallucinations without worsening motor function[174]
- pimavanserin (Nuplazid)
- FDA-approved to treat hallucinations & delusions in patients with Parkinson's disease
- improves psychosis without affecting motor function[174]
- quetiapine (Seroquel)
- helps control hallucinations without worsening motor function
- associated with a decline in cognitive function
- serotonin 2A receptor (HTR2A) antagonists may be of benefit[40]
- quetiapine & clozapine have some HTR2A antagonism
- cyproheptadine, trazodone
- avoid using high-affinity dopamine receptor antagonists (haloperidol, risperidone ..) in patients with Parkinson's disease[119]
- may worsen cognition
- may result in neuroleptic malignant syndrome
- quetiapine preferred agent for patients with Parkinson's disease[119]
- avoid antipsychotics with anticholinergic activity[41]
- cholinesterase inhibitors may be of benefit[14]
- antipsychotic use in Parkinson's disease associated with increased risk of mortality (RR=2.35)[90]
- neurosurgery
- stereotactic surgery to place lesions in the ventral lateral thalamus may be beneficial in cases of severe tremor
- unilateral pallidotomy for patients not responding to medication
- focused ultrasound ablation of the posteroventral globus pallidus internus opposite the most symptomatic Parkinson's disease side[173]
- MRI-guided unilateral ultrasound subthalamotomy may benefit patients with asymmetric Parkinson's disease[107]
- deep brain stimulation
- benefit for patients with sustained response to Sinemet, but use limited by adverse effects[6]
- wearing off of Sinemet not responsive to optimizing medication management[6]
- benefit to treatment-refractory cases[35]
- subthalamic nucleus stimulation may be superior to globus pallidus pars interna stimulation[53]
- may benefit selected patients early in the course of Parkinson's disease[54]
- may be of benefit in 'off state' central pain[79]
- adaptive deep brain stimulation may improve symptoms of Parkinson's disease[109]
- worse quality-of-life score before deep brain stimulation associated with greater improvement at 2 years[126]
- benefit for patients with sustained response to Sinemet, but use limited by adverse effects[6]
- transcranial image-guided focused ultrasound
- assistive devices for fall prevention
- patients with Parkinson's disease often have a tendency to fall backwards & do best with front wheel walkers[16][69]
- 4 wheel walkers also increase risk of falling due to fenistation
- GRS11 states 4 wheeled walker increases stability & promote a forward position that would prevent a backward fall[16]
- standard walkers (without wheels) tend to increase freezing
- treat constipation with isosmotic polyethylene glycol[38]
- treat depression[21]
- rasagiline added to an SSRI may improve mood & cognition[77]
- avoid antidepressants with anticholinergic activity (tricyclic antidpressants)
- telephone-based cognitive behavioral therapy effective for treatment of depression[139]
- nabilone may improve anxiety & sleep disorders[3]
- cognitive therapy may improve functional disability[75]
- cognitive behavioral therapy may benefit patients with impulse control disorder (impulsive behavior)[55]
- does not improve depressive symptoms or apathy[75]
- beneficial effects of cognitive training are small but statistically significant[86]
- working memory, processing speed, & executive function improve
- global cognition, overall memory, visuospatial skills, & depressive symptoms do not
- regular exercise with attention to posture[15]
- encourage physical activity for all patients[6]
- a healthy diet & physical activity may improve outcomes[162]
- Tai chi may be of benefit[46]
- resistance training may be of benefit
- stretching is recommended[46]
- low-intensity aerobic exercise (treadmill) improves gait instability & cardiovascular fitness[51]
- walking (70-80% of maximum heart rate) 3 times/week for 45 minutes improves aerobic fitness, motor function, cognition, & quality of life[74]
- early exercise & other regular physical activity both associated with slower clinical decline[160]
- exercise recommendations should be individualized[16]
- weekly dance training slows progression of motor & non-motor symptoms[150]
- timed get-up & go test may be preferred functional assessment tool[16]
- encourage physical activity for all patients[6]
- rehabilitation & palliative care
- offer rehabilative therapy options[91]
- physical therapy of benefit[49]; may be of benefit[16][56]
- combination of physical therapy & occupational therapy of no benefit[88]
- outpatient multidisciplinary palliative care program associated with short-term improvements in quality of life[138]
- excessive daytime somnolence, sleep attacks
- disease may impair ability to operate motor vehicle[27]
- modafinil 200-400 mg/day
- methylphenidate may be useful for fatigue[38]
- abuse is potentially a problem[38]
- no evidence of effectiveness for hypersomnolence due to sleep disturbance[16]
- melatonin 50 mg QHS shows statistically significant improvement in total sleep time, but small improvement may not be clinically significant[67]
- sildenafil for erectile dysfunction[38]
- alternative therapy
- moving to music rather than a metronome better supports entrainment & control[133]
- acupuncture may improve gait in Parkinson disease patients[156]
- diet high in flavonoid-rich foods linked to lower mortality risk in persons with Parkinson's disease[158]
- unproven therapies
- creatine does not slow progression of Parkinson's disease[78]
- caffeine of no benefit for tremor motor symptoms[96][105]
- monoclonal antibodies targeting alpha-synuclein (Cinpanemab & Prasinezumab) of no benefit[164][165]
- simvastatin of no benefit as Parkinson's disease-modifying agent[167]
- nicotine patches do not slow progression of early Parkinson's disease[186]
- annual skin examination[39]
- neurology consult:
- care provided by a neurologist reduces hospitalizations, results in shorter hospitalizations, & reduces overall care costs[52]
- telemedicine for virtual house calls for Parkinson disease is feasible & with similar quality-of-life outcomes to those of traditional office-visit approach[98]
- surgery in patients with Parkinson's disease
- withholding Parkinson agents for surgery (Sinemet &/or dopaminergic receptor agonists) may result in parkinsonism-hyperpyrexia syndrome
- management includes restarting Parkinson agents[6]
- withholding Parkinson agents for surgery (Sinemet &/or dopaminergic receptor agonists) may result in parkinsonism-hyperpyrexia syndrome
- prognosis:
- most symptoms can be effectly managed for years
- within 5 years of Sinemet or dopamine agonist treatment, 50% of patients will develop motor fluctuations or dyskinesias[6]
- timed get-up & go test may be preferred functional assessment tool[16]
- mortality similar to patients without Parkinson's disease[15]
- most symptoms can be effectly managed for years
- compensation strategies for patients with Parkinson's disease
- advance directives discussion[91]
- prevention:
- MIND diet & Mediterranean diet may delay onset of Parkinson's disease[145]
- a healthful plant-based diet with the inclusion of vegetables, nuts & tea may be associated with a lower risk of Parkinson's disease[181]
* catechol O-methyltransferase (COMT)
Comparative biology
- induced pluripotent stem cell-derived dopaminergic progenitors functioned as midbrain dopaminergic neurons in Macaca fascicularis treated with the neurotoxin MPTP[102]
- the mature dopaminergic neurons extended dense neurites into the striatum
- an increase in spontaneous movement of the monkeys after transplantation observed
- no neoplasms noted within 2 years
- in mice, Parkinson's disease can begin with formation of pathological alpha-synuclein in the gut, which travels up the vagus nerve to the brain[130]
Notes
- health care providers diagnosing or providing treatment to Parkinson's disease patients are now required to report each case of Parkinson's disease to the California Department of Public Health[128]
More general terms
More specific terms
Additional terms
- deep brain stimulation (DBS)
- diagnostic criteria for Parkinson's disease
- investigational treatment of Parkinson's disease
- orthostatic hypotension in Parkinson's disease
- parkinson plus syndrome
- Parkinson's dementia; Parkinson's psychosis-dementia complex
- Parkinson's disease 2, juvenile, autosomal recessive
- pharmacologic agents for treatment of Parkinson's disease
- staging of Parkinson's disease (Hoehn-Yahr scale)
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed., Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY 1995, pg 731
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1050-52
- ↑ 3.0 3.1 3.2 Lang AE & Lozano AM Parkinson's disease. First of two parts. N Engl J Med 339:1044, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9761807
- ↑ Lang AE & Lozano AM Parkinson's disease. Second of two parts. N Engl J Med 339:1130, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9770561
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 390
- ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 6.29 6.30 6.31 6.32 6.33 6.34 6.35 6.36 6.37 6.38 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Prescriber's Letter 6(10):57, Oct, 1999 (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Ross GW et al Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10819950
George J Does Caffeine Protect Against Parkinson's? - Benefit seen even for people with Parkinson's genetic risk MedPage Today September 30, 2020 https://www.medpagetoday.com/neurology/parkinsonsdisease/88893
Crotty GF, Maciuca R, Macklin EA et al Association of caffeine and related analytes with resistance to Parkinson's disease among LRRK2 mutation carriers: A metabolomic study. Neurology 2020. Sept 30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32999056 https://n.neurology.org/content/early/2020/09/30/WNL.0000000000010863 - ↑ Lang AE & Lozano AM Parkinson's disease. First of two parts. N Engl J Med 339:1044, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9761807
Lang AE & Lozano AM Parkinson's disease. Second of two parts. N Engl J Med 339:1130, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9770561 - ↑ 10.0 10.1 Prescribers Letter 8(8):45, 2001 (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 Bronstein J, UCLA Department of Neurology, Parkinson Syllabus, 2001
- ↑ 12.0 12.1 Journal Watch 22(4):32, 2002 Hobson et al Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 287:455, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11798367
- ↑ 13.0 13.1 Prescriber's Letter 9(3):17 2002 (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 Wolters EC & Berendse HW Management of psychosis in Parkinson's disease. Current Opinion in Neurology 2001,14:499 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11470967
- ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 25-28, 2002 Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 17.0 17.1 Prescriber's Letter 9(11):65 2002 (subscription needed) http://www.prescribersletter.com http://www.ninds.nih.gov/news_and_events/pressrelease_parkinsons_coenzymeq10_101402.htm
- ↑ 18.0 18.1 Prescriber's Letter 10(8):45 2003 (subscription needed) http://www.prescribersletter.com
- ↑ Journal Watch 25(1):11, 2005 Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K; Parkinson Study Group. Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2498-508. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15590952
- ↑ 20.0 20.1 Avorn J, Schneeweiss S, Sudarsky LR, Benner J, et al Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol. 2005 Aug;62(8):1242-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16087765
- ↑ 21.0 21.1 21.2 21.3 Park M, Ross GW, Petrovitch H, White LR, Masaki KH, Nelson JS, Tanner CM, Curb JD, Blanchette PL, Abbott RD. Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Neurology. 2005 Mar 22;64(6):1047-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15781824
- ↑ 22.0 22.1 de Lau LM et al, Serum uric acid levels and the risk of Parkinson disease. Ann Neurol 2005, 58:797 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16240356
- ↑ 23.0 23.1 Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol. 2005 Dec;58(6):963-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16240369
Wahner AD et al, Non-steroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007, 69:1836 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17984451 - ↑ 24.0 24.1 Internal Medicine News 39(8): April 15, 2006
- ↑ Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):968-75. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16606907
Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):976-82. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16606908
Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte- Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):983-95. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16606909
Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, Shulman LM, Gronseth G, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):996-1002. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16606910 - ↑ 26.0 26.1 Benbir G et al, Features associated with the development of hallucinations in Parkinson's disease Acta Neurol Scand 2006, 114:239 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16942542
- ↑ 27.0 27.1 Uc EY et al, Driving with distraction in Parkinson's disease. Neurology 2006, 67:1774 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17130409
- ↑ 28.0 28.1 Ascherio A et al, Pesticide exposure and risk for Parkinson's disease. Ann Neurol 2006, 60:197 Baldereschi M, Inzitari M, Vanni P, Di Carlo A, Inzitari D.
Pesticide exposure might be a strong risk factor for Parkinson's disease. Ann Neurol. 2007 May 8; [Epub ahead of print] No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17487876
Dick FD. Parkinson's disease and pesticide exposures. Br Med Bull. 2006;79-80:219-31. Epub 2007 Jan 22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17242039 [PubMed - in process]
Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Neurochem. 2007 Mar;100(6):1469-79. Epub 2007 Jan 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17241123 [PubMed - indexed for MEDLINE]
Gomez C, Bandez MJ, Navarro A. Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome. Front Biosci. 2007 Jan 1;12:1079-93. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17127363 - ↑ 29.0 29.1 Braak H, Rub U, Schultz C, Del Tredici K. Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases. J Alzheimers Dis. 2006;9(3 Suppl):35-44. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16914843
Braak H, Del Tredici K. Invited Article: Nervous system pathology in sporadic Parkinson disease. Neurology 2008; 70:1916 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18474848 - ↑ 30.0 30.1 Murata M, Hasegawa K, Kanazawa I; The Japan Zonisamide on PD Study Group. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17200492
- ↑ 31.0 31.1 Klein C et al, Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol 2007, 6:652-62 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17582365
- ↑ 32.0 32.1 Rocca WA et al, Increased risk of parkinsonism in women who underwent oophorectomy before menopause Neurology 2007, 69:1074 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17761549
- ↑ 33.0 33.1 Becker C, Jick SS, Meier CR. Use of antihypertensives and the risk of Parkinson disease. Neurology. 2008 Feb 6; [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/18256367
- ↑ 34.0 34.1 Katzenschlager R et al. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology 2008 Aug 12; 71:474. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18579806
Weiner WJ and Reich SG. Agonist or levodopa for Parkinson disease?: Ultimately, it doesn't matter; neither is good enough. Neurology 2008 Aug 12; 71:470. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18695156 - ↑ 35.0 35.1 Weaver FM et al, Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease JAMA. 2009;301(1):63-73 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19126811
- ↑ 36.0 36.1 Troiano AR et al. PET demonstrates reduced dopamine transporter expression in PD with dyskinesias. Neurology 2009 Apr 7; 72:1211. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19020294
Vingerhoets FJG. Dyskinesia in Parkinson disease: Back for the future? Neurology 2009 Apr 7; 72:1202. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19349599 - ↑ 37.0 37.1 Olanow CW et al, A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease N Engl J Med 2009, 361:1268 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19776408 <Internet> http://content.nejm.org/cgi/content/short/361/13/1268
- ↑ 38.0 38.1 38.2 38.3 38.4 Zesiewicz TA et al Practice Parameter: Treatment of nonmotor symptoms of Parkinson disease NEUROLOGY 2010;74:924-931 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20231670 <Internet> http://www.neurology.org/cgi/content/full/74/11/924
- ↑ 39.0 39.1 39.2 Bertoni JM et al. Increased melanoma risk in Parkinson disease: A prospective clinicopathological study. Arch Neurol 2010 Mar; 67:347. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20212233
- ↑ 40.0 40.1 40.2 Ballanger B et al. Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 2010 Apr; 67:416. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20385906
- ↑ 41.0 41.1 41.2 Ehrt U et al. Use of drugs with anticholinergic effect and impact on cognition in Parkinson's disease: A cohort study. J Neurol Neurosurg Psychiatry 2010 Feb; 81:160. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19770163
Starkstein SE. Anticholinergic activity and cognitive decline in Parkinson's disease. J Neurol Neurosurg Psychiatry 2010 Feb; 81:129. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20145024 - ↑ 42.0 42.1 42.2 Tysnes O-B et al Are dysautonomic and sensory symptoms present in early Parkinson's disease? Acta Neurol Scand 2010 Jul; 122:Suppl 190:72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20586740
- ↑ Driver JA et al Use of non-steroidal anti-inflammatory drugs and risk of Parkinson's disease: Nested case-control study. BMJ 2011 Jan 20; 342:d198 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21252104
- ↑ 44.0 44.1 44.2 International Parkinson Disease Genomics Consortium. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: A meta-analysis of genome-wide association studies. Lancet 2011 Feb 19; 377:641. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21292315
- ↑ Prescriber's Letter 18(9): 2011 CHART: Comparison of Parkinson's Disease Drugs CHART: Parkinson's Disease Therapy Algorithm Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270920&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 46.0 46.1 46.2 Li F et al. Tai chi and postural stability in patients with Parkinson's disease. N Engl J Med 2012 Feb 9; 366:511. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22316445
- ↑ Physician's First Watch for April 5, 2012 Massachesetts Medical Society
- ↑ 48.0 48.1 Gjerstad MD et al. Increased risk of leg motor restlessness but not RLS in early Parkinson disease. Neurology 2011 Nov 29; 77:1941. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22076542
- ↑ 49.0 49.1 Tomlinson CL et al. Physiotherapy intervention in Parkinson's disease: Systematic review and meta-analysis. BMJ 2012 Aug 6; 345:e5004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22867913
- ↑ 50.0 50.1 50.2 50.3 Scullin MK et al. Nocturnal sleep enhances working memory training in Parkinson's disease but not Lewy body dementia. Brain 2012 Sep; 135:2789. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22907117
- ↑ 51.0 51.1 Shulman LM et al Randomized Clinical Trial of 3 Types of Physical Exercise for Patients With Parkinson Disease Arch Neurol. 2012, Nov 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23128427 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1389386
Rosenthal LS and Dorsey ER The Benefits of Exercise in Parkinson Disease Arch Neurol. 2012, Nov <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23117841 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1389387
Mehrholz J, Friis R, Kugler J, Twork S, Storch A, Pohl M. Treadmill training for patients with Parkinson's disease. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007830 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20091652 - ↑ 52.0 52.1 Willis AW et al. Neurologist-associated reduction in PD-related hospitalizations and health care expenditures. Neurology 2012 Oct 23; 79:1774. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23054239
- ↑ 53.0 53.1 Odekerken VJJ et al Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): A randomised controlled trial. Lancet Neurol 2012 Nov 16; PMID: https://www.ncbi.nlm.nih.gov/pubmed/23168021
- ↑ 54.0 54.1 Schuepbach WMM et al Neurostimulation for Parkinson's Disease with Early Motor Complications. N Engl J Med 2013; 368:610-622February 14, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23406026 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1205158
Tanner CM A Second Honeymoon for Parkinson's Disease? N Engl J Med 2013; 368:675-676February 14, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23406033 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1214913 - ↑ 55.0 55.1 55.2 Okai D et al. Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers. Neurology 2013 Jan 16 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23325911 <Internet> http://www.neurology.org/content/80/9/792
Macphee GJA and Carson A. Impulse control disorders in Parkinson disease: Is cognitive-behavior therapy worth a wager? Neurology 2013 Jan 16 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23325905 <Internet> http://www.neurology.or g/content/80/9/782 - ↑ 56.0 56.1 van Nimwegen M et al. Promotion of physical activity and fitness in sedentary patients with Parkinson's disease: Randomised controlled trial. BMJ 2013 Mar 1; 346:f576 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23457213
- ↑ Rao G, Fisch L, Srinivasan S et al Does this patient have Parkinson disease? JAMA. 2003 Jan 15;289(3):347-53. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12525236
- ↑ Morley JF, Hurtig HI. Current understanding and management of Parkinson disease: five new things. Neurology. 2010 Nov 2;75(18 Suppl 1):S9-15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21041778
- ↑ Messina D, Cerasa A, Condino F et al Patterns of brain atrophy in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord. 2011 Mar;17(3):172-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21236720
- ↑ 60.0 60.1 Palfi S et al Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412048 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961939-X/abstract
Stoessl AJ Gene therapy for Parkinson's disease: a step closer? The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412047 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962108-X/fulltext - ↑ 61.0 61.1 Eng ML, Welty TE. Management of hallucinations and psychosis in Parkinson's disease. Am J Geriatr Pharmacother. 2010 Aug;8(4):316-30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20869621
- ↑ 62.0 62.1 Weintraub D, Chen P, Ignacio RV, Mamikonyan E, Kales HC. Patterns and trends in antipsychotic prescribing for Parkinson disease psychosis. Arch Neurol. 2011 Jul;68(7):899-904 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21747029
- ↑ Olanow CW et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: A randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014 Feb; 13:141 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24361112
- ↑ Cheng EM, Tonn S, Swain-Eng R et al Quality improvement in neurology: AAN Parkinson disease quality measures: report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology. Neurology. 2010 Nov 30;75(22):2021-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21115958
- ↑ Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009 May 26;72(21 Suppl 4):S1-136. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19470958
- ↑ 66.0 66.1 66.2 Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease. Mov Disord. 2003 Mar;18(3):287-93. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12621632
- ↑ 67.0 67.1 Dowling GA, Mastick J, Colling E et al Melatonin for sleep disturbances in Parkinson's disease. Sleep Med. 2005 Sep;6(5):459-66. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16084125
- ↑ 68.0 68.1 68.2 Ondo WG, Fayle R, Atassi F, Jankovic J. Modafinil for daytime somnolence in Parkinson's disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1636-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16291885
- ↑ 69.0 69.1 Constantinescu R, Leonard C, Deeley C, Kurlan R. Assistive devices for gait in Parkinson's disease. Parkinsonism Relat Disord. 2007 Apr;13(3):133-8. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16914362
Cubo E, Moore CG, Leurgans S, Goetz CG. Wheeled and standard walkers in Parkinson's disease patients with gait freezing. Parkinsonism Relat Disord. 2003 Oct;10(1):9-14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14499200 - ↑ 70.0 70.1 Ishihara L, Brayne C. A systematic review of depression and mental illness preceding Parkinson's disease. Acta Neurol Scand. 2006 Apr;113(4):211-20. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16542159
- ↑ 71.0 71.1 71.2 Manor Y, Balas M, Giladi N, Mootanah R, Cohen JT. Anxiety, depression and swallowing disorders in patients with Parkinson's disease. Parkinsonism Relat Disord. 2009 Jul;15(6):453-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19071054
- ↑ 72.0 72.1 72.2 PD MED Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): A large, open-label, pragmatic randomised trial. Lancet 2014 Jun 11; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24928805 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60683-8/fulltext
Lang AE and Marras C. Initiating dopaminergic treatment in Parkinson's disease. Lancet 2014 Jun 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24928806 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60962-4/fulltext - ↑ Faust-Socher A et al. Enhanced creative thinking under dopaminergic therapy in Parkinson disease. Ann Neurol 2014 Jun; 75:935 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24816898
- ↑ 74.0 74.1 Uc EY et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology 2014 Jul 29; 83:413 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24991037 <Internet> http://www.neurology.org/content/83/5/413
- ↑ 75.0 75.1 75.2 Pena J et al. Improving functional disability and cognition in Parkinson disease: Randomized controlled trial. Neurology 2014 Dec 2; 83:2167 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25361785
- ↑ 76.0 76.1 76.2 76.3 Schrag A et al. Prediagnostic presentations of Parkinson's disease in primary care: A case-control study. Lancet Neurol 2015 Jan; 14:57 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25435387 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2814%2970287-X/abstract
- ↑ 77.0 77.1 Smith KM et al. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO Study: Effects on nonmotor symptoms and tolerability. JAMA Neurol 2014 Nov 24 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25420207 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1934721
- ↑ 78.0 78.1 Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: A randomized clinical trial. JAMA 2015 Feb 10; 313:584 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25668262 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2108890
- ↑ 79.0 79.1 Jung YJ et al. An 8-year follow-up on the effect of subthalamic nucleus deep brain stimulation on pain in Parkinson disease. JAMA Neurol 2015 Mar 23 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25799451 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2210915
- ↑ 80.0 80.1 Gardner RC et al. Traumatic brain injury in later life increases risk for Parkinson's disease. Ann Neurol 2015 Feb 27 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25726936 <Internet> http://onlinelibrary.wiley.com/doi/10.1002/ana.24396/abstract
- ↑ 81.0 81.1 81.2 Gustafsson H et al. Depression and subsequent risk of Parkinson disease: A nationwide cohort study. Neurology 2015 May 20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25995056
- ↑ Fox SH, Katzenschlager R, Lim SY et al The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2011 Oct;26 Suppl 3:S2-41 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22021173
- ↑ Ghosh R1, Liddle BJ. Emergency presentations of Parkinson's disease: early recognition and treatment are crucial for optimum outcome. Postgrad Med J. 2011 Feb;87(1024):125-31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21106801
- ↑ Seppi K1, Weintraub D, Coelho M et al The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease. Mov Disord. 2011 Oct;26 Suppl 3:S42-80 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22021174
- ↑ 85.0 85.1 Stoessl AJ, Martin WW, McKeown MJ, Sossi V. Advances in imaging in Parkinson's disease. Lancet Neurol. 2011 Nov;10(11):987-1001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22014434
- ↑ 86.0 86.1 Leung IH, Walton CC, Hallock H et al. Cognitive training in Parkinson disease: A systematic review and meta-analysis. Neurology 2015 Nov 24; 85:1843. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26519540
- ↑ 87.0 87.1 Henderson EJ, Lord SR, Brodie MA et al Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo- controlled, phase 2 trial. Lancet Neurology. Jan 12, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26795874 <Internet> http://thelancet.com/journals/laneur/article/PIIS1474-4422%2815%2900389-0/abstract
Moreau C, Devos D, Defebvre L Acetylcholinesterase inhibitors and gait: a steadying hand? Lancet Neurology. Jan 12, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26795875 <Internet> http://thelancet.com/journals/laneur/article/PIIS1474-4422%2816%2900003-X/abstract - ↑ 88.0 88.1 Clarke CE et al Physiotherapy and Occupational Therapy vs No Therapy in Mild to Moderate Parkinson Disease. JAMA Neurol. Published online January 19, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26785394 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2482646
Ahlskog JE New and Appropriate Goals for Parkinson Disease Physical Therapy. JAMA Neurol. Published online January 19, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26785221 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2482644 - ↑ 89.0 89.1 Egeberg A et al. Exploring the association between rosacea and Parkinson disease: A Danish nationwide cohort study. JAMA Neurol 2016 Mar 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26999031
- ↑ 90.0 90.1 Weintraub D et al. Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurol 2016 Mar 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26999262
- ↑ 91.0 91.1 91.2 91.3 91.4 91.5 Factor SA et al. Quality improvement in neurology: Parkinson disease update quality measurement set. Executive summary. Neurology 2016 May 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27170564
- ↑ 92.0 92.1 92.2 Melville NA Statin Use Linked to Increased Parkinson's Risk. Medscape. Oct 26, 2016 http://www.medscape.com/viewarticle/870996
- ↑ 93.0 93.1 Centi J et al. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology 2016 Nov 30; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27903817
Boylan LS, Messinis L. Orthostatic hypotension, cognition, and Parkinson disease: Dumbing down by standing up. Neurology 2016 Nov 30; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27903812 - ↑ 94.0 94.1 Gever J The Lysosome: Viable Target for Parkinson's? Glucocerebrosidase activity may provide novel approach to stubborn illness. MedPage Today. April 23, 2017 https://www.medpagetoday.com/MeetingCoverage/AAN/64736
- ↑ 95.0 95.1 95.2 Okun MS Truncal Vagotomy Reduces Parkinson Disease Risk. NEJM Journal Watch. April 26, 2017 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Liu B, Fang F, Pedersen NL et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology 2017 Apr 26 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28446653 <Internet> http://www.neurology.org/content/early/2017/04/26/WNL.0000000000003961 - ↑ 96.0 96.1 Fiore K Caffeine No Help for Motor Function in Parkinson's - Randomized controlled trial clashes with epidemiologic data. MedPage Today. June 09, 2017 https://www.medpagetoday.com/MeetingCoverage/MDS/65907
- ↑ 97.0 97.1 Anderson P More Evidence Links High Cholesterol to Lower Parkinson's Risk. Medscape - Jun 14, 2017. http://www.medscape.com/viewarticle/881576
- ↑ 98.0 98.1 Beck CA, Beran DB, Biglan KM et al. National randomized controlled trial of virtual house calls for Parkinson disease. Neurology 2017 Aug 16 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28814455 <Internet> http://www.neurology.org/content/early/2017/08/16/WNL.0000000000004357
- ↑ 99.0 99.1 Brooks M FDA Clears First Drug for Parkinson's Dyskinesia Medscape - Aug 25, 2017. http://www.medscape.com/viewarticle/884697
- ↑ 100.0 100.1 Athauda D, Maclagan K, Skene SS et al. Exenatide once weekly versus placebo in Parkinson's disease: A randomised, double-blind, placebo-controlled trial. Lancet 2017 Aug 3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28781108
- ↑ 101.0 101.1 Lowe D A New Piece of the Parkinson's Puzzle. Science Translational Medicine. Sept 5, 2017 http://blogs.sciencemag.org/pipeline/archives/2017/09/05/a-new-piece-of-the-parkinsons-puzzle
- ↑ 102.0 102.1 Kikuchi T, Morizane A, Doi D et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model. Nature 2017 Aug 31; 548:592. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28858313 <Internet> http://www.nature.com/nature/journal/v548/n7669/full/nature23664.html
- ↑ 103.0 103.1 Chen H, Shrestha S, Huang X et al. Olfaction and incident Parkinson disease in US white and black older adults. Neurology 2017 Sep 6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28878051
- ↑ NINDS Parkinson's Disease Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-disease-Information-Page
Depression and Parkinson's Disease http://www.nimh.nih.gov/publicat/depparkinson.cfm - ↑ 105.0 105.1 Postuma RB, Anang J, Pelletier A et al. Caffeine as symptomatic treatment for Parkinson disease (Cafe-PD): A randomized trial. Neurology 2017 Sep 27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28954882
- ↑ 106.0 106.1 Cumming K, Macleod AD, Myint PK, Counsell CE. Early weight loss in parkinsonism predicts poor outcomes: Evidence from an incident cohort study. Neurology 2017 Nov 28; 89:2254 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29079685 Free PMC Article
- ↑ 107.0 107.1 Martinez-Fernandez R, Rodriguez-Rojas R, Del Alamo M et al. Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: A pilot study. Lancet Neurol 2018 Jan; 17:54 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29203153
- ↑ 108.0 108.1 108.2 Darweesh SKL, Wolters FJ, Postuma RB et al. Association between poor cognitive functioning and risk of incident parkinsonism: The Rotterdam Study. JAMA Neurol 2017 Dec 1; 74:1431 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28973176
- ↑ 109.0 109.1 Arlotti M, Marceglia S, Foffani G Eight-hours adaptive deep brain stimulation in patients with Parkinson disease. Neurology. February 14, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29444973 <Internet> http://n.neurology.org/content/early/2018/02/14/WNL.0000000000005121
- ↑ 110.0 110.1 Dirkx MF, Zach H, Bloem BR, Hallett M, Helmich RC. The nature of postural tremor in Parkinson disease. Neurology 2018 Mar 27; 90:e1095. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29476038
- ↑ 111.0 111.1 Tremor Disorder or Parkinson's - YouTube https://www.youtube.com/watch?v=-Y3kex_8UoY
- ↑ 112.0 112.1 Villumsen M, Aznar S, Pakkenberg B et al Inflammatory bowel disease increases the risk of Parkinson's disease: a Danish nationwide cohort study 1977-2014. Gut. May 21, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29785965 <Internet> http://gut.bmj.com/content/early/2018/04/16/gutjnl-2017-315666
- ↑ 113.0 113.1 113.2 113.3 113.4 113.5 Walker M. Bacteriophages: Hidden Players in Parkinson's Disease? Viruses affect microbiome composition, perhaps fostering rogue neural proteins. MedPage Today. June 13, 2018
Tetz G, Tetz V Bacteriophages: are they an overlooked driver of Parkinson's disease? ASM Microbe 2018; Abstract 117 - SUNDAY. http://www.abstractsonline.com/pp8/#!/4623/presentation/11102
Tetz G, Brown SM, Hao Y, Tetz V. Parkinson's disease and bacteriophages as its overlooked contributors. Sci Rep 2018 Jul 17; 8:10812 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30018338 Free PMC Article https://www.nature.com/articles/s41598-018-29173-4 - ↑ 114.0 114.1 George J. Type 2 Diabetes Tied to Subsequent Risk of PD. Risk of Parkinson's later in life higher among younger T2D patients. MedPage Today. June 13, 2018 https://www.medpagetoday.com/neurology/parkinsonsdisease/73479
De Pablo-Fernandez E, Goldacre R, Pakpoor J et al Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study. Neurology 2018; June 13. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29898968 <Internet> http://n.neurology.org/content/early/2018/06/13/WNL.0000000000005771 - ↑ 115.0 115.1 Knudsen K, Fedorova TD, Hansen AK et al. In-vivo staging of pathology in REM sleep behaviour disorder: A multimodality imaging case-control study. Lancet Neurol 2018 Jun 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29866443
- ↑ 116.0 116.1 Corvol JC, Artaud F, Cormier-Dequaire F et al. Longitudinal analysis of impulse control disorders in Parkinson disease. Neurology. 2018 Jul 17;91(3):e189-e201. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29925549 <Internet> http://n.neurology.org/content/91/3/e189
- ↑ 117.0 117.1 117.2 George J, Solomon HA, Caputo D. Can Eyes Predict Parkinson's Disease? Dopamine loss tied to retinal thinning; may be early disease biomarker. MedPage Today. August 15, 2018 https://www.medpagetoday.com/neurology/parkinsonsdisease/74575
Ahn J, Lee JY, Kim TW et al Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. Aug 15, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30111550 <Internet> http://n.neurology.org/content/early/2018/08/15/WNL.0000000000006157
Adams JL, La Morgia C The search for Parkinson disease biomarkers. Retinal thinning as a correlate of dopamine loss. Neurology. Aug 15, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30111551 <Internet> http://n.neurology.org/content/early/2018/08/15/WNL.0000000000006148 - ↑ 118.0 118.1 Fang X, Han D, Cheng Q et al Association of Levels of Physical Activity With Risk of Parkinson Disease. A Systematic Review and Meta-analysis. JAMA Network Open. 2018;1(5):e18242 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2703134
Nelson LM Physical Activity and Parkinson Disease RiskAn Intriguing Link. JAMA Network Open. 2018;1(5):e182633 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2703129 - ↑ 119.0 119.1 119.2 Samudra N, Patel N, Womack KB, Khemani P, Chitnis S. Psychosis in Parkinson Disease: A Review of Etiology, Phenomenology, and Management. Drugs Aging. 2016 Dec;33(12):855-863. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27830568
- ↑ Canning CG, Paul SS, Nieuwboer A. Prevention of falls in Parkinson's disease: a review of fall risk factors and the role of physical interventions. Neurodegener Dis Manag. 2014;4(3):203-21. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25095816
- ↑ 121.0 121.1 121.2 121.3 Killinger BA, Madaj1 Z, Sikora JW et al The vermiform appendix impacts the risk of developing Parkinson's disease. Science Translational Medicine. 31 Oct 2018: 10(465) eaar5280 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30381408 <Internet> http://stm.sciencemag.org/content/10/465/eaar5280
- ↑ Mantri S, Fullard M, Gray SL et al. Patterns of dementia treatment and frank prescribing errors in older adults with Parkinson disease. JAMA Neurol 2018 Oct 1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/3028504 https://jamanetwork.com/journals/jamaneurology/fullarticle/2704469
- ↑ 123.0 123.1 Backstrom D, Granasen G, Domellof ME, et al. Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study. Neurology 2018 Nov 27;91(22):e2045-e2056. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30381367
- ↑ 124.0 124.1 124.2 George J Early Levodopa Neither Protective Nor Harmful in Parkinson's - Early treatment shows no disease-modifying effect at 80 weeks. MedPage Today. January 24, 2019 https://www.medpagetoday.com/neurology/parkinsonsdisease/77613
Verschuur CVM, Suwijn SR, Boel JA et al Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease. N Engl J Med 2019; 380:315-324 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30673543 https://www.nejm.org/doi/full/10.1056/NEJMoa1809983
Bressman S, Saunders-Pullman R. When to Start Levodopa Therapy for Parkinson's Disease. N Engl J Med 2019; 380:389-390 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30673551 https://www.nejm.org/doi/full/10.1056/NEJMe1814611 - ↑ 125.0 125.1 Trenkwalder C et al. Increased dose of carbidopa with levodopa and entacapone improves "off" time in a randomized trial. Neurology 2019 Mar 26; 92:e1487 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30824559
- ↑ 126.0 126.1 Schuepach WMM, Tonder L, Schnitzler A et al. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease. Neurology 2019 Mar 5; 92:e1109-e1120 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30737338
- ↑ 127.0 127.1 Christine CW, Bankiewicz KS, Van Laar AD et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease. Ann Neurol. 2019 May;85(5):704-714. Epub 2019 Mar 26. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30802998 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25450
Christine CW, Richardson RM, Van Laar AD et al. Safety of AADC gene therapy for moderately advanced Parkinson disease: Three-year outcomes from the PD-1101 trial. Neurology 2021 Oct 14; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34649873 https://n.neurology.org/content/early/2021/10/14/WNL.0000000000012952 - ↑ 128.0 128.1 128.2 Pasquini J, Durcan R, Wiblin L et al. Clinical implications of early caudate dysfunction in Parkinson's disease. J Neurol Neurosurg Psychiatry 2019 May 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31079063 Free Article
- ↑ California Parkinson's Disease Registry Data Submission Deadline The Medical Board of California. June 19, 2019 webmaster@mbc.ca.gov
- ↑ 130.0 130.1 Kim S, Kwon SH, Kam TI et al. Transneuronal propagation of pathologic alpha-synuclein from the gut to the brain models Parkinson's disease. Neuron 2019 Jun 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31255487 https://www.cell.com/neuron/fulltext/S0896-6273(19)30488-X
- ↑ 131.0 131.1 131.2 Fereshtehnejad SM, Yao C, Pelletier A et al. Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: A prospective study. Brain 2019 Jul; 142:2051 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31111143
- ↑ 132.0 132.1 Wilson H, Dervenoulas G, Pagano G et al. Serotonergic pathology and disease burden in the premotor and motor phase of A53T alpha-synuclein parkinsonism: A cross-sectional study. Lancet Neurol 2019 Jun 19 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31229470 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30140-1/fulltext
- ↑ 133.0 133.1 Tumolo J Music Enhances Control in Adults With PD Annals of Long-Term Care. Oct 13, 2019 https://www.managedhealthcareconnect.com/content/music-enhances-control-adults-pd
Rose D, Delevoye-Turrell Y, Ott L, Annett LE, Lovatt PJ. Music and metronomes differentially impact motor timing in people with and without Parkinson's disease: effects of slow, medium, and fast tempi on entrainment and synchronization performances in finger tapping, toe tapping, and stepping on the spot tasks Parkinsons Dis. 2019 August 18;2019:6530838 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31531220 Free PMC Article - ↑ Hiorth YH, Pedersen KF, Dalen I, Tysnes OB, Alves G. Orthostatic hypotension in Parkinson disease: A 7-year prospective population-based study. Neurology 2019 Oct 15; 93:e1526. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31527282 https://n.neurology.org/content/93/16/e1526
- ↑ 135.0 135.1 135.2 135.3 Hughes KC, Gao X, Molsberry S et al. Physical activity and prodromal features of Parkinson disease. Neurology 2019 Dec 3; 93:e2157 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31719136
- ↑ 136.0 136.1 Olanow CW, Factor SA, Espay AJ et al Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol. 2019 Dec 6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31818699 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30396-5/fulltext
- ↑ 137.0 137.1 137.2 Zarkali A, McColgan P, Leyland LA et al. Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction. Neurology 2020 Feb 24; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/32094242 https://n.neurology.org/content/early/2020/02/23/WNL.0000000000009014
- ↑ 138.0 138.1 Kluger BM, Miyasaki J, Katz M et al. Comparison of integrated outpatient palliative care with standard care in patients with Parkinson disease and related disorders: A randomized clinical trial. JAMA Neurol 2020 Feb 10; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/32040141 Free PMC Article https://jamanetwork.com/journals/jamaneurology/fullarticle/2760511.
- ↑ 139.0 139.1 Dobkin RD, Mann SL, Gara MA et al. Telephone-based cognitive behavioral therapy for depression in Parkinson disease: A randomized controlled trial. Neurology 2020 Apr 21; 94:e1764 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32238507 https://n.neurology.org/content/94/16/e1764
- ↑ 140.0 140.1 Bryois J, Skene NG, Hansen TF et al Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease. Nature Genetics volume 52, pages 482-493 (2020) PMID: https://www.ncbi.nlm.nih.gov/pubmed/32341526 https://www.nature.com/articles/s41588-020-0610-9
- ↑ 141.0 141.1 Wen MC et al Apathy is associated with white matter network disruption and specific cognitive deficits in Parkinson's disease. Psychological Medicine. Published online: 11 June 2020 https://www.cambridge.org/core/journals/psychological-medicine/article/apathy-is-associated-with-white-matter-network-disruption-and-specific-cognitive-deficits-in-parkinsons-disease/5DD37E359EEA9A8D0D39393C848DBDAC
- ↑ 142.0 142.1 Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson DiseaseA Review. JAMA. 2020;323(6):548-560 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32044947 https://jamanetwork.com/journals/jama/fullarticle/2760741
- ↑ Peball M, Krismer F, Knaus HG et al. Non-motor symptoms in Parkinson's disease are reduced by nabilone. Ann Neurol 2020 Aug 5; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/32757413 https://onlinelibrary.wiley.com/doi/10.1002/ana.25864
- ↑ 144.0 144.1 Murueta-Goyena A et al. Retinal thickness predicts the risk of cognitive decline in Parkinson Disease. Ann Neurol 2021 Jan; 89:165. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33098308 PMCID: PMC7756646 Free PMC article https://onlinelibrary.wiley.com/doi/10.1002/ana.25944
- ↑ 145.0 145.1 Metcalfe-Roach A, Yu AC, Golz E et al MIND and Mediterranean Diets Associated with Later Onset of Parkinson's Disease. Movement Disorders. 2021. Jan 6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33404118 https://onlinelibrary.wiley.com/doi/10.1002/mds.28464
- ↑ 146.0 146.1 George J HDL Cholesterol Linked to Parkinson's Disease - Population study shows relationships between HDL levels and variability with incident PD MedPage Today February 5, 2021 https://www.medpagetoday.com/neurology/parkinsonsdisease/91084
Park JH, Lee CW, Nam MJ et al Association of High-density Lipoprotein Cholesterol Variability and the Risk of Developing Parkinson's Disease. Neurology 2021. Feb 3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33536275 https://n.neurology.org/content/early/2021/02/03/WNL.0000000000011553 - ↑ 147.0 147.1 Hantikainen E et al. Dietary antioxidants and the risk of Parkinson disease: The Swedish National March Cohort. Neurology 2021 Feb 9; 96:e895 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33408141 https://n.neurology.org/content/96/6/e895
- ↑ 148.0 148.1 Jo S, Kim YJ, Park KW et al Association of NO2 and Other Air Pollution Exposures With the Risk of Parkinson Disease. JAMA Neurol. 2021;78(7):800-808. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33999109 PMCID: PMC8129903 (available on 2022-05-17) https://jamanetwork.com/journals/jamaneurology/fullarticle/2780249
- ↑ 149.0 149.1 149.2 Tisza MJ, Buck CB. A catalog of tens of thousands of viruses from human metagenomes reveals hidden associations with chronic diseases. Proc Natl Acad Sci U S A 2021 Jun 8; 118:e2023202118. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34083435 PMCID: PMC8201803 Free PMC article https://www.pnas.org/content/118/23/e2023202118
- ↑ 150.0 150.1 Tumolo J Weekly Dance Training Slows Parkinson Disease Impairment. Annals of Long-Term Care. July 26, 2021 https://www.hmpgloballearningnetwork.com/site/altc/news/weekly-dance-training-slows-parkinson-disease-impairment
Bearss KA, DeSouza JFX. Parkinson's disease motor symptom progression slowed with multisensory dance learning over 3-years: a preliminary longitudinal investigation. Brain Sci. 2021;11(7):895. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34356129 PMCID: PMC8303681 Free PMC article - ↑ 151.0 151.1 Oonk NGM, Movig KLL, van der Palen J et al. The Impact of Non-dopaminergic Medication on Quality of Life in Parkinson's Disease. Clin Drug Investig. 2021 Aug 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34374959 https://link.springer.com/article/10.1007%2Fs40261-021-01064-z
- ↑ 152.0 152.1 152.2 Jeong SH, Lee HS, Chung SJ, et al. Effects of statins on dopamine loss and prognosis in Parkinson's disease. Brain 2021 Aug 4; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34347020 https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awab292/6339771
- ↑ 153.0 153.1 McMillan JM, Michalchuk Q, Goodarzi Z. Frailty in Parkinson's disease: A systematic review and meta-analysis. Clin Park Relat Disord. 2021;4:100095. May 25. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34316672 PMCID: PMC8299963 Free PMC article
- ↑ Tosserams A, Wit L, Sturkenboom IHWM et al. Perception and use of compensation strategies for gait impairment by persons with Parkinson Disease. Neurology 2021 Oct 5; 97:e1404. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34497067 PMCID: PMC8520387 Free PMC article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520387/
- ↑ George J Focused Ultrasound Approved for Advanced Parkinson's. Expanded indication includes medication-refractory PD patients with motor problems. MedPage Today November 5, 2021 https://www.medpagetoday.com/neurology/parkinsonsdisease/95458
- ↑ 156.0 156.1 Pereira CR, Criado MB, Machado J et al Acute effects of acupuncture in balance and gait of Parkinson disease patients - a preliminary study. Complement Ther Clin Pract. 2021;45:101479 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34543873
- ↑ 157.0 157.1 Tumolo J Intense Balance Training May Affect Brain Structure in Parkinson Disease. Annals of Long-Term Care. Jan 18, 2022 https://www.hmpgloballearningnetwork.com/site/altc/news/intense-balance-training-may-affect-brain-structure-parkinson-disease
Albrecht F, Pereira JB, Mijalkov M, et al. Effects of a highly challenging balance training program on motor function and brain structure in Parkinson's disease. J Parkinsons Dis. 2021;11(4):2057-2071. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34511513 PMCID: PMC8673526 DOI: Free PMC article - ↑ 158.0 158.1 George J More Flavonoids, Better Parkinson's Outcome. MedPage Today January 26, 2022 https://www.medpagetoday.com/neurology/parkinsonsdisease/96878
Anderson P Berries, Red Wine Linked to Lower Mortality in Parkinson's Disease. Medscape. Jan 26, 2022 https://www.medscape.com/viewarticle/967313
Zhang X. Molsberry SA, Yeh TS et al. Intake of flavonoids and flavonoid-rich foods, and mortality risk among individuals with Parkinson disease: A prospective cohort study. Neurology 2022 Jan 26; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35082171 https://n.neurology.org/content/early/2022/01/26/WNL.0000000000013275 - ↑ 159.0 159.1 159.2 Gray R, Patel S, Ives N et al. Long-term effectiveness of adjuvant treatment with catechol-O-methyltransferase or monoamine oxidase B inhibitors compared with dopamine agonists among patients with Parkinson disease uncontrolled by levodopa therapy: The PD MED randomized clinical trial. JAMA Neurol 2021 Dec 28; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/34962574 PMCID: PMC8715387 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2787405
- ↑ 160.0 160.1 Tsukita K et al. Long-term effect of regular physical activity and exercise habits in patients with early Parkinson disease. Neurology 2022 Feb 22;98(8):e859-e871 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35022304 PMCID: PMC8883509 Free PMC article https://n.neurology.org/content/98/8/e859
- ↑ 161.0 161.1 161.2 Pass W Is Copper Culpable in Parkinson's Disease? Medscape. July 21, 2022 https://www.medscape.com/viewarticle/977686
Synhaivska O, Bhattacharya S, Campioni S et al Single-Particle Resolution of Copper-Associated Annular alpha-Synuclein Oligomers Reveals Potential Therapeutic Targets of Neurodegeneration. ACS Chem. Neurosci. 2022, 13, 9, 1410-1421 https://pubs.acs.org/doi/10.1021/acschemneuro.2c00021 - ↑ 162.0 162.1 Zhang X et al. Association of diet and physical activity with all-cause mortality among adults with Parkinson disease. JAMA Netw Open 2022 Aug 1; 5:e2227738 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35984656 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2795409
- ↑ 163.0 163.1 Pagano G et al. Trial of prasinezumab in early-stage Parkinson's disease. N Engl J Med 2022 Aug 4;387:421. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35921451 https://www.nejm.org/doi/10.1056/NEJMoa2202867
Whone A. Monoclonal antibody therapy in Parkinson's disease - The end? N Engl J Med 2022 Aug 4;387:466. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35921458 https://www.nejm.org/doi/10.1056/NEJMe2207681 - ↑ 164.0 164.1 Pagano G, Taylor KI, Anzures-Cabrera J et al Trial of Prasinezumab in Early-Stage Parkinson's Disease. N Engl J Med 2022; 387:421-432. August 4, PMID: https://www.ncbi.nlm.nih.gov/pubmed/35921451 https://www.nejm.org/doi/full/10.1056/NEJMoa2202867
- ↑ 165.0 165.1 Lang A, Siderowf AD, Macklin EA et al Trial of Cinpanemab in Early Parkinson's Disease. N Engl J Med 2022; 387:408-420. Aug 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35921450 https://www.nejm.org/doi/full/10.1056/NEJMoa2203395
- ↑ 166.0 166.1 Otaiku AI Distressing dreams, cognitive decline, and risk of dementia: A prospective study of three population-based cohorts. eClinicalMedicine, 2022. Sept 21 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00370-4/fulltext
- ↑ 167.0 167.1 Stevens KN, Creanor S, Jeffery A et al Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease. A Randomized Clinical Trial. JAMA Neurol. Published online October 31, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36315128 https://jamanetwork.com/journals/jamaneurology/fullarticle/2797508
- ↑ 168.0 168.1 168.2 Tumolo J Dysphagia for Medication Common Among Patients With Parkinson Disease. Annals of Long-Term Care. Nov 28, 2022 https://www.hmpgloballearningnetwork.com/site/altc/news/dysphagia-medication-common-among-patients-parkinson-disease
Labeit B, Berkovich E, Claus I et al. Dysphagia for medication in Parkinson's disease. NPJ Parkinsons Dis. 2022;8(1):156. Nov 12. https://www.nature.com/articles/s41531-022-00421-9 - ↑ 169.0 169.1 169.2 169.3 George J Parkinson's Incidence 50% Higher Than Previously Thought. Clusters of Parkinson's disease cases seen in certain U.S. regions. MedPage Today December 15, 2022 https://www.medpagetoday.com/neurology/parkinsonsdisease/102267
Willis AW, Roberts E, Beck JC et al Incidence of Parkinson disease in North America NPJ Parkinsons Dis. 2022. 8:170. Dec 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36522332 PMCID: PMC9755252 Free PMC article https://www.nature.com/articles/s41531-022-00410-y - ↑ 170.0 170.1 170.2 Miller-Patterson C et al. Functional impairment in individuals with prodromal or unrecognized Parkinson disease. JAMA Neurol 2022 Dec 19; [e-pub]. https://jamanetwork.com/journals/jamaneurology/fullarticle/2799605
Bledsoe IO et al. Functional impairment preceding Parkinson disease diagnosis - What's in a prodrome? JAMA Neurol 2022 Dec 19; [e-pub] https://jamanetwork.com/journals/jamaneurology/fullarticle/2799603 - ↑ 171.0 171.1 171.2 Kneisel K Epilepsy Drugs May Up Risk of Parkinson's. Strongest association seen for sodium valproate. MedPage Today December 27, 2022 https://www.medpagetoday.com/neurology/seizures/102398
Belete D, Jacobs BM, Simonet C et al Association Between Antiepileptic Drugs and Incident Parkinson Disease in the UK Biobank. JAMA Neurol. Published online December 27, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36574240 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799620 - ↑ 172.00 172.01 172.02 172.03 172.04 172.05 172.06 172.07 172.08 172.09 172.10 172.11 172.12 172.13 172.14 172.15 172.16 172.17 172.18 172.19 172.20 Schrag A, Bohlken J, Dammertz L et a Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease. JAMA Neurol. 2023;80(2):161-171 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36342675 PMCID: PMC9641600 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2798380
- ↑ 173.0 173.1 Krishna V et al. Trial of globus pallidus focused ultrasound ablation in Parkinson's disease. N Engl J Med 2023 Feb 23; 388:683-693. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36812432 https://www.nejm.org/doi/10.1056/NEJMoa2202721
- ↑ 174.0 174.1 174.2 Yunusa I, Rashid N, Seyedin R, Paratane D, Rajagopalan K. Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis. J Geriatr Psychiatry Neurol. 2023 Jan 31:8919887231154933. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36720473
- ↑ 175.0 175.1 Dorsey ER, Zafar M, Lettenberger SE et al Trichloroethylene: An Invisible Cause of Parkinson's Disease? Journal of Parkinson's Disease. 2023 13(2):203-218. March 14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36938742 https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd225047
- ↑ 176.0 176.1 176.2 Flores-Torres MH et al Long-Term Intake of Folate, Vitamin B6, and Vitamin B12 and the Incidence of Parkinson's Disease in a Sample of U.S. Women and Men. Movement Disorders. 2023. March 20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36938854 https://movementdisorders.onlinelibrary.wiley.com/doi/abs/10.1002/mds.29383
- ↑ George J Parkinson's Biomarker Shows High Accuracy. Assay identifies hallmark protein and could help diagnose people earlier. MedPage Today April 12, 2023 https://www.medpagetoday.com/neurology/parkinsonsdisease/103990
Siderowf A, Concha-Marambio L, Lafontant DE et al Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using alpha-synuclein seed amplification: a cross- sectional study. Lancet Neurol. 2023 May;22(5):407-417. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37059509 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00109-6/fulltext - ↑ 178.0 178.1 178.2 178.3 178.4 Goldman SM, Weaver FM, Stroupe KT et al Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune. JAMA Neurol. Published online May 15, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37184848 https://jamanetwork.com/journals/jamaneurology/fullarticle/2805037
- ↑ 179.0 179.1 179.2 179.3 Wagner SK, Romero-Bascones D, Cortina-Borja M et al Retinal Optical Coherence Tomography Features Associated With Incident and Prevalent Parkinson Disease. Neurology. 2023. August 21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37604659 https://n.neurology.org/content/early/2023/08/21/WNL.0000000000207727
- ↑ 180.0 180.1 Konings B, VillatoroL, Van den Eynde J et al Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases. Gut. 2023 Aug 24;gutjnl-2023-329685 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37620120 https://gut.bmj.com/content/early/2023/07/12/gutjnl-2023-329685
- ↑ 181.0 181.1 Tresserra-Rimbau A, Thompson AS, Bondonno N et al Plant-Based Dietary Patterns and Parkinson's Disease: A Prospective Analysis ofthe UK Biobank. Movement Disorders. 2023. August 21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37602951 https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29580
- ↑ 182.0 182.1 Homayoun H. Parkinson disease. Ann Intern Med. 2018;169:ITC33-ITC48. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30178019
- ↑ 183.0 183.1 183.2 Giladi N et al. Safety and efficacy of venglustat in GBA1-associated Parkinson's disease: An international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2023 Aug; 22:661. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37479372 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00205-3/fulltext
- ↑ 184.0 184.1 184.2 Palacios N et al. Metagenomics of the gut microbiome in Parkinson's disease: Prodromal changes. Ann Neurol 2023 Jun 14; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37314861 https://onlinelibrary.wiley.com/doi/10.1002/ana.26719
- ↑ 185.0 185.1 Pereira JB, Kumar A, Hall S et al DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease. Nat Aging 2023. Sept 18 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37723208 https://www.nature.com/articles/s43587-023-00478-y
- ↑ 186.0 186.1 Oertel WH et al. Transdermal nicotine treatment and progression of early Parkinson's disease. NEJM Evid 2023 Aug 22; [e-pub]. Not indexed in PubMed https://evidence.nejm.org/doi/10.1056/EVIDoa2200311
- ↑ 187.0 187.1 Beorchia S When Digestive Symptoms Signal Parkinson's Disease. Medscape. Oct 20, 2023 https://www.medscape.com/viewarticle/997576
- ↑ Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33848468 Review.
- ↑ 189.0 189.1 Yan S, Chang C, Janzen A et al. Neuronally derived extracellular vesicle alpha-synuclein as a serum biomarker for individuals at risk of developing Parkinson disease. JAMA Neurol 2024 Jan 1; 81:59-68. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38048087 PMCID: PMC10696516 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2812433
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