Neurodegeneration

Neurodegeneration is progressive loss of specific neuronal populations. The affected cells determine the clinical pattern: dopamine-producing neurons are vulnerable in Parkinson disease (PD), while networks supporting memory and cognition are progressively disrupted in Alzheimer disease (AD). Misfolded proteins and abnormal protein aggregates are common pathological themes, but the bedside syndromes are not interchangeable. In PD, dopaminergic neurons in the substantia nigra pars compacta degenerate, reducing dopamine delivery to the striatum. Alpha-synuclein aggregates form Lewy body pathology. With less dopamine available to regulate basal-ganglia motor circuits, movement becomes difficult to initiate and scale. The characteristic motor syndrome is bradykinesia plus rigidity and/or a resting tremor. A patient may describe a hand tremor while sitting quietly, difficulty turning in bed, smaller handwriting, reduced arm swing, a soft voice, or freezing when approaching a doorway. Postural instability and falls often become more prominent as disease advances. PD is not only a movement disorder. Constipation, urinary symptoms, orthostatic hypotension, depression, sleep disturbance, excessive daytime sleepiness, hallucinations, dysphagia, and impulse-control behaviours may influence safety more than the tremor does. A patient who is walking adequately...