REVIEWS Ageing, neurodegeneration and Parkinson’s

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 pres-entation 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