Parkinson's Disease & Parkinson's Disease Dementia

Definition

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms due to dopaminergic neuron loss in the substantia nigra. Parkinson’s Disease Dementia (PDD) refers to cognitive decline that develops in the context of established PD.

Epidemiology

• PD prevalence: ~1–2% in individuals over 60 years.
• Incidence increases with age; mean onset around 60 years.
• Slight male predominance (M:F ~3:2).
• PDD occurs in 50–80% of PD patients over long-term follow-up.
• Genetic forms account for ~10–15% of cases; sporadic disease is more common.

Etiology

• Idiopathic (most common), multifactorial: genetic, environmental, and aging-related factors.
• Genetic mutations: SNCA, LRRK2, PARK2, PARK7, PINK1 associated with familial PD.
• Environmental exposures: pesticides, heavy metals, head trauma may increase risk.
• Oxidative stress, mitochondrial dysfunction, and neuroinflammation contribute to neurodegeneration.

Pathophysiology

• Loss of dopaminergic neurons in the substantia nigra pars compacta.
• Dopamine deficiency in the striatum leads to motor dysfunction (bradykinesia, rigidity, tremor).
• Formation of Lewy bodies (α-synuclein aggregates) in neurons.
• Cholinergic deficits and cortical Lewy body deposition contribute to Parkinson’s Disease Dementia.
• Impaired basal ganglia circuitry leads to characteristic motor symptoms.