Product information and disease description Place of product in therapy Disease description

Definition and etiology

13 evidence topics · 8 sources

Clinical and pathological definition of Parkinson's disease

“Parkinson’s disease (PD) is a complex age-related neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits.” (opens the source at this quote in a new tab)
“Pathologically, PD is defined by loss of dopaminergic neurons in the substantia nigra pars compacta (SN) located in the midbrain and associated with Lewy bodies, which are cytoplasmic inclusions that include insoluble alpha-synuclein aggregates.” (opens the source at this quote in a new tab)
“The clinical diagnosis of PD is based primarily on motor features, such as a slowly progressive asymmetric resting tremor, cogwheel rigidity and bradykinesia, although non-motor features, which include anosmia, constipation, depression and REM sleep behavior disorder, can develop years before motor deficits.” (opens the source at this quote in a new tab)

Parkinsonism as the core clinical feature

“Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity.” (opens the source at this quote in a new tab)
“Parkinsonism is defined as bradykinesia, in combination with either rest tremor, rigidity, or both. These features must be clearly demonstrable and not attributable to confounding factors.” (opens the source at this quote in a new tab)
“Bradykinesia is defined as slowness of movement AND decrement in amplitude or speed (or progressive hesitations/halts) as movements are continued.” (opens the source at this quote in a new tab)
“Although bradykinesia also occurs in voice, face, and axial/gait domains, limb bradykinesia must be documented to establish a diagnosis of PD.” (opens the source at this quote in a new tab)
“Rest tremor refers to a 4- to 6-Hz tremor in the fully resting limb, which is suppressed during movement initiation.” (opens the source at this quote in a new tab)
“Although postural instability is a feature of parkinsonism, it is not part of the MDS-PD criteria for parkinsonism caused by PD.” (opens the source at this quote in a new tab)
“This is reflected in a new diagnostic classification, prodromal PD, which is considered to be a true stage of PD (ie, prodromal PD is PD).” (opens the source at this quote in a new tab)

Parkinson's disease among the parkinsonian disorders

“Parkinsonism, the clinical term for a disorder with prominent bradykinesia and variable associated extrapyramidal signs and symptoms, is accompanied by degeneration of the nigrostriatal dopaminergic system, with neuronal loss and reactive gliosis in the substantia nigra found at autopsy.” (opens the source at this quote in a new tab)
“PD is but one of a host of parkinsonian disorders” (opens the source at this quote in a new tab)

Clinical indicators of advanced Parkinson's disease

“Lack of a global consensus on the definition of advanced Parkinson's disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care.” (opens the source at this quote in a new tab)
“Key indicators of APD included: (i) motor-moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h "off" symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor-mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment-repeated falls despite optimal treatment, and difficulty with activities of daily living.” (opens the source at this quote in a new tab)

Age as a risk factor

“Indeed, the single greatest risk factor for PD is advanced age” (opens the source at this quote in a new tab)

Multifactorial etiology and heritability

“Most PD cases likely have a multifactorial etiology, resulting from the combined effects of environmental and genetic factors.” (opens the source at this quote in a new tab)
“Although identifiable mutations in certain genes cause PD in around 5–10% of cases, these mutations are absent in most people with PD.” (opens the source at this quote in a new tab)
“A study comparing concordance rates in monozygotic and dizygotic twins estimated the heritability of PD to be only 30%, suggesting that the majority of PD risk is related to environmental and behavioral factors” (opens the source at this quote in a new tab)

Genetic etiology: LRRK2 and GBA variants

“Mutations in the LRRK2 gene are associated with autosomal dominant PD with incomplete penetrance (about 25% for the G2019S mutation, but much higher for the R144G mutation), and are present in about 1 to 2 percent of all PD patients and 5% in familial PD, but higher in some populations such as patients of Ashkenazi Jewish ancestry and in North African Berbers” (opens the source at this quote in a new tab)
“Carriers of a GBA mutation have an approximately 4-fold increased risk of PD, although the risk varies with different GBA mutations.” (opens the source at this quote in a new tab)

Genetic etiology: causal and risk variants across ancestries

“We analysed genome and exome sequencing and genotyping data of 99,783 individuals, including 58,559 individuals with PD and 41,224 controls, from eleven different genetically inferred ancestries” (opens the source at this quote in a new tab)
“Overall, ~2% (1217/58559) of individuals with Parkinson’s disease carried a causal variant, with substantial variations across ancestries ranging from ~0·5% (10/2844 and 3/550) in African and African-Admixed to ~7% (92/1347) in Middle Eastern and >10% (251/2343) Ashkenazi Jewish ancestries.” (opens the source at this quote in a new tab)
“Risk variants in GBA1 and LRRK2 were identified in 11·8% (6893/58559) of individuals with Parkinson’s disease and 8·7% (3578/41224) of controls.” (opens the source at this quote in a new tab)

Genetic etiology: monogenic forms and polygenic risk

“In most populations, 3–5% of Parkinson’s disease is explained by genetic causes linked to known Parkinson’s disease genes, thus representing monogenic Parkinson’s disease, whereas 90 genetic risk variants collectively explain 16–36% of the heritable risk of non-monogenic Parkinson’s disease.” (opens the source at this quote in a new tab)
“Mutations in PRKN and PINK1 are the major causes of autosomal recessive and early-onset Parkinson’s disease, with the frequent PRKN mutations accounting for up to 77% of cases of juvenile Parkinson’s disease (age of onset being younger than 20 years) and 10–20% of young-onset Parkinson’s disease.” (opens the source at this quote in a new tab)
“pathogenic GBA variants occurred in 8·5% of people with Parkinson’s disease in a multi-ethnic sample of more than 1100 individuals.” (opens the source at this quote in a new tab)

Genetic etiology: proportion of genetic cases by age at onset

“Young-onset Parkinson disease is commonly defined by an age of onset <45 years and >10% of those individuals have a genetic basis, and the proportion of genetically defined cases rises to >40% of those with disease onset before 30 years of age” (opens the source at this quote in a new tab)

Environmental etiology: pesticides and other exposures

“In studies spanning many decades in numerous populations worldwide, pesticide exposure, farm work or rural residence have been associated with an increased PD risk” (opens the source at this quote in a new tab)
“Occupational exposure as well as “passive” exposure due to residence near to pesticide treated fields is associated with a greater risk of PD.” (opens the source at this quote in a new tab)
“Pesticides associated with PD, including paraquat, rotenone, 2,4-D and several dithiocarbamates and organochlorines, cause experimental parkinsonism in laboratory studies, supporting the possibility that these associations reflect causal effects” (opens the source at this quote in a new tab)

Factors associated with lower risk: tobacco and caffeine

“The most consistent association is a reduced risk of PD in cigarette smokers and, in a few studies, other tobacco users” (opens the source at this quote in a new tab)
“Coffee drinking and caffeine use are also associated with a lower risk of PD” (opens the source at this quote in a new tab)

Family history, constipation, non-smoking, and other associated factors

“Additional causal associations include having a relative with Parkinson’s disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson’s disease.” (opens the source at this quote in a new tab)
“Negative associations with the risk of developing Parkinson’s disease include smoking, coffee drinking, anti-inflammatory drug use, high plasma urate levels, or physical activity.” (opens the source at this quote in a new tab)