Brain and cognitive reserve.

The concept of reserve is well-recognized in medicine. Various organs of the body, for example the kidney and the liver, manifest reserve such that significant damage can occur to the organ without impacting on clinical function. The very fact that an individual can donate one kidney and yet remain healthy attests to this fact. The glomerular filtration rate (GFR) is generally considered to be a measure of the excretory function of the kidney, with the normal GFR being 90 mL/min/1.73 m. Significant kidney damage can occur without affecting GFR, and the GFR is generally 30 mL/min/1.73 m before features of chronic renal failure are manifest. The brain is recognized to demonstrate a similar reserve capacity. It is known that degeneration of dopamine cells in the substantia nigra starts long before the symptoms of Parkinson’s disease develop, and the absolute number of pigmented neurons has been reported to be reduced to about one-third in patients. Individuals with brain injury appear to have different thresholds at which they will develop clinical symptoms. This reserve capacity has received the greatest attention in the case of Alzheimer disease. An early report showed that some individuals with high levels of Alzheimer’s type pathology in their brains escaped dementia during life, and that this was related to higher counts of large pyramidal neurons in their cerebral cortices. This led to the more commonly held conceptualization of brain reserve, that is, the so-called “hard” or “neurological” brain reserve. According to the hard brain reserve concept, individuals differ in their reserve capacity depending upon some characteristics of the brains they are endowed with. Early support for this came from studies that related greater head size, measured as head circumference or intracranial volume, to a reduced risk of dementia. The argument presented was that larger brains were able to tolerate a greater extent of pathology before they reached the functional threshold at which symptoms became clinically manifest, that is, they had further to fall before reaching the disorder threshold. Head size is a proxy measure for brain size before the onset of pathology, but its appeal is limited by the fact that its association with intelligence or cognitive capacity is generally poor. Further studies showed that the relationship between head circumference and dementia was restricted to those in the low to very low range of head girth, or to an interaction with the polymorphism on the apolipoprotein E gene. It was also not clear what constituted the basis of a large brain. Was it large neuronal numbers, increased dendritic proliferation, greater synaptic density, more white matter connections, or simply large ventricles? A major limitation of the “large brain” concept of reserve is that it is a static and passive viewpoint. An approach that Perneczky et al. take in this issue is to relate the brain’s reserve capacity to its metabolic activity rather than the size. They use fluoro-2deoxy-glucose positron emission tomography to examine relative metabolic activity in different brain regions. In previous studies, metabolic activity has been shown to be better related to functional capacity than brain size, and Perneczky et al. have again demonstrated a significant association between glucose hypometabolism and impaired activities of daily living, especially for the right temporoparietal cortex. Furthermore, their study takes the concept of brain reserve as being dynamic and active, and subject to