Abstract
An aging-related reduction in the brain's functional reserve may explain why delirium is more frequent in the elderly than in younger people insofar as the reserve becomes inadequate to cover the metabolic requirements that are critically increased by stressors. The aim of this paper is to review the normal aging-related changes that theoretically compromise complex mental activities, neuronal and synaptic densities, and the neurocomputational flexibility of the functional reserve. A pivotal factor is diminished connectivity, which is substantially due to the loss of synapses and should specifically affect association systems and cholinergic fibres in delirious patients. However, micro-angiopathy with impaired blood flow autoregulation, increased blood/brain barrier permeability, changes in cerebrospinal fluid dynamics, weakened mitochondrial performance, and a pro-inflammatory involution of the immune system may also jointly affect neurons and their synaptic assets, and even cause the progression of delirium to dementia regardless of the presence of co-existing plaques, tangles, or other pathological markers. On the other hand, the developmental growth in functional reserve during childhood and adolescence makes the brain increasingly resistant to delirium, and residual reserve can allow the elderly to recover. These data support the view that functional reserve is the variable that confronts stressors and governs the risk and intensity of and recovery from delirium. Although people of any age are at risk of delirium, the elderly are at greater risk because aging and age-dependent structural changes inevitably affect the brain's functional reserve.