Ageing, neurodegeneration, and Parkinson’s disease.
Age is the largest risk factor for the development and progression of Parkinson’s disease (PD). Ageing affects many cellular processes that predispose to neurodegeneration, and age-related changes in cellular function predispose to the pathogenesis of PD. The accumulation of age-related somatic damage combined with a failure of compensatory mechanisms may lead to an acceleration of PD with age. The formation of Lewy bodies may represent a marker for protective mechanisms against age-related dysfunction and degeneration of the nervous system. Mild parkinsonian signs may be present in older people, which are associated with reduced function. These may be due to age-related decline in dopaminergic activity, incidental Lewy body disease, degenerative pathologies (early PD and Alzheimer’s disease) or vascular pathology. Ageing may affect the clinical presentation of PD with altered drug side effects, increased risk of developing dementia and an increased likelihood of admission to a nursing home. Progression of PD, including the development of dementia, and hallucinations is related to the age of the patient rather than the age of disease onset. PD may reflect a failure of the normal cellular compensatory mechanisms in vulnerable brain regions, and this vulnerability is increased by ageing. PD is one of the best examples of an age-related disease.
Age Ageing. 2010 Mar;39(2):156-61
Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity.
The goal of this study was to estimate the incidence of Parkinson’s disease by age, gender, and ethnicity. Newly diagnosed Parkinson’s disease cases in 1994-1995 were identified among members of the Kaiser Permanente Medical Care Program of Northern California, a large health maintenance organization. Each case met modified standardized criteria/Hughes diagnostic criteria as applied by a movement disorder specialist. Incidence rates per 100,000 person-years were calculated using the Kaiser Permanente membership information as the denominator and adjusted for age and/or gender using the direct method of standardization. A total of 588 newly diagnosed (incident) cases of Parkinson’s disease were identified, which gave an overall annualized age- and gender-adjusted incidence rate of 13.4 per 100,000 (95% confidence interval (CI): 11.4, 15.5). The incidence rapidly increased over the age of 60 years, with only 4% of the cases being under the age of 50 years. The rate for men (19.0 per 100,000, 95% CI: 16.1, 21.8) was 91% higher than that for women (9.9 per 100,000, 95% CI: 7.6, 12.2). The age- and gender-adjusted rate per 100,000 was highest among Hispanics (16.6, 95% CI: 12.0, 21.3), followed by non-Hispanic Whites (13.6, 95% CI: 11.5, 15.7), Asians (11.3, 95% CI: 7.2, 15.3), and Blacks (10.2, 95% CI: 6.4, 14.0). These data suggest that the incidence of Parkinson’s disease varies by race/ethnicity.
Am J Epidemiol. 2003 Jun 1;157(11):1015-22
Prevalence of parkinsonian signs and associated mortality in a community population of older people.
BACKGROUND: Older people frequently have signs of parkinsonism, but information about the prevalence of parkinsonism and mortality among those with the condition in the community is limited. METHODS: A stratified random sample of 467 residents of East Boston, Massachusetts, 65 years of age or older, were given structured neurologic examinations. Using uniform, specified combinations of parkinsonian signs, we estimated the prevalence of four categories of signs--bradykinesia, gait disturbance, rigidity, and tremor--and of parkinsonism, defined as the presence of two or more categories. We did not study Parkinson’s disease because it could not be distinguished from other conditions that can cause parkinsonism. Proportional-hazards models were used to compare the risk of death among people with and those without parkinsonism. RESULTS: One hundred fifty-nine persons had parkinsonism, 301 did not, and 7 could not be classified. The overall prevalence estimates were 14.9% for people 65 to 74 years of age, 29.5% for those 75 to 84, and 52.4% for those 85 and older. With a mean follow-up period of 9.2 years, 124 persons with parkinsonism (78 percent) and 146 persons without (49%) died. Adjusted for age and sex, the overall risk of death among people with parkinsonism was 2.0 (95% confidence interval, 1.6 to 2.6) times that among people without. Among people with parkinsonism, the presence of gait disturbance was associated with an increased risk of death. CONCLUSIONS: Parkinsonism is very common among people over the age of 65, and its prevalence increases markedly with age. Parkinsonism is associated with a twofold increase in the risk of death, which is strongly related to the presence of a gait disturbance.
N Engl J Med. 1996 Jan 11;334(2):71-6
Parkinson’s disease: clinical features and diagnosis.
OBJECTIVE: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. METHODS: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease,” “diagnosis” and “signs and symptoms.” RESULTS: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. CONCLUSIONS: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76
Parkinson’s disease as multifactorial oxidative neurodegeneration: implications for integrative management.
Parkinson’s disease (PD) is the most common movement pathology, severely afflicting dopaminergic neurons within the substantia nigra (SN) along with non-dopaminergic, extra-nigral projection bundles that control circuits for sensory, associative, premotor, and motor pathways. Clinical, experimental, microanatomic, and biochemical evidence suggests PD involves multifactorial, oxidative neurodegeneration, and that levodopa therapy adds to the oxidative burden. The SN is uniquely vulnerable to oxidative damage, having high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate. Oxidative phosphorylation abnormalities impair energetics in the SN mitochondria, also intensifying oxygen free radical generation. These pro-oxidative factors combine within the SN dopaminergic neurons to create extreme vulnerability to oxidative challenge. Epidemiologic studies and long-term tracking of victims of MPTP (1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine) poisoning, suggest oxidative stress compounded by exogenous toxins may trigger the neurodegenerative progression of PD. Rational, integrative management of PD requires: (1) dietary revision, especially to lower calories; (2) rebalancing of essential fatty acid intake away from pro-inflammatory and toward anti-inflammatory prostaglandins; (3) aggressive repletion of glutathione and other nutrient antioxidants and cofactors; (4) energy nutrients acetyl L-carnitine, coenzyme Q10, NADH, and the membrane phospholipid phosphatidylserine (PS), (5) chelation as necessary for heavy metals; and (6) liver P450 detoxification support.
Altern Med Rev. 2000 Dec;5(6):502-29
Mitochondrial dysfunction and oxidative damages in the molecular pathology of Parkinson’s disease.
Parkinson’s disease is a complex disease characterized by a progressive degeneration of nigrostriatal dopaminergic neurons. Development of this condition is defined by interaction between the genetic constitution of an organism and environmental factors. The analysis of the genes associated with development of monogenic forms of disease, has allowed pointing out proteasome degradation, the differentiation of dopaminergic neurons, the mitochondrial dysfunction and oxidative damage. In this review a variety of data which indicate on a key role of the mitochondrial dysfunction and oxidative stress in Parkinson’s disease pathogenesis will be more detail considered.
Mol Biol (Mosk). 2008 Sep-Oct;42(5):809-19