Premorbid brain size is a determinant of functional reserve in abstinent crack-cocaine and crack-cocaine-alcohol-dependent adults.

Studies of Alzheimer's disease patients show that individuals with larger premorbid brains have a later onset of disease, or a lessened severity of cognitive impairment, or both. This may be due to a "functional reserve" associated with the greater number of neurons and synapses available in larger brains. We used magnetic resonance imaging and the MicroCog Assessment of Cognitive Functioning to examine the association between intracranial volume (premorbid brain size) and neuropsychological function in abstinent crack-cocaine and crack-cocaine-alcohol dependent individuals. There were no significant differences between the crack-only and the crack-alcohol dependent participants in neuropsychological performance or in intracranial volume. The abstinent cocaine-dependent individuals (both crack-only and crack-alcohol) were significantly impaired in many neuropsychological domains. Intracranial volume accounted for a significant proportion of the variance in neuropsychological performance. This result is consistent with the finding in the Alzheimer's literature that larger brains can maintain function to a greater degree, or for a longer period of time, in the face of cerebral disease or insult. Functional reserve may be a heretofore little recognized protective mechanism of the brain that has consequences for the severity of expression of cerebral disease or insult throughout life.