The cognitive abilities of older persons vary dramatically. There are tell tale signs in the brain that doctors use to make a definitive diagnosis of Alzheimer Disease (AD). These are referred to as "plaques" and "tangles." When they achieve a threshold degree and distribution, the neuropathologist doing the examination establishes that the brain findings are consistent with the diagnosis of AD. Interestingly, it has been established in many studies that approximately 40% of the subjects whose brains house this degree of pathology on post mortem exam have no evidence of mental impairment. This suggests that some brains are able to tolerate these potentially devastating findings much better than others. The "Million Dollar Question" is why. At present, the neurobiologic basis for this robust observation is not well understood.
The concept of "compensation" is commonly applied to many organ systems throughout the body and is an important determinant of health outcomes. When a relative donates a kidney, for example, the donor experiences no loss of renal function because of the large amount of reserve function in the remaining kidney. Hence, it easily compensated for the loss of its neighbor. The only change observed is that it may enlarge slightly over ensuing months due to enhanced physiologic demands. Is it possible that similar changes can occur in the brain.
Brain transplants have not been performed, at least yet. However, interesting findings noted on functional brain scans such as PET (Positron Emission Tomography) scans and fMRI (functional Magnetic Resonance Imaging) scans suggest there is an innate ability of one part of the brain to compensate for diminished function elsewhere. Thus, the brain, de facto, has a component of brain reserve. This is consistent with the notion that the functional organization of the brain is felt to be redundant. In addition, it has been postulated that there are differences between brains in their efficiency and ability to respond to certain environmental challenges.
Neuroimaging data of the type just mentioned support this view. When performing a cognitive task, aging is associated with lower activation of brain regions used by young subjects while performing the same task, and increased activation in other regions. This phenomenon has been interpreted as demonstrating compensation by alternate networks. Surprisingly, a similar pattern of brain activation has been observed in both young patients with mild AD and older subjects without AD. The implication is that the process of compensation (manifested by the engagement of additional brain resources) is a normal process during aging and in pathologic states such as AD (and presumable stroke, head injury and other disease states).
The concept of brain reserve was first referenced in a study of individuals with high levels of AD pathology post mortem who remained nondemented in life and had almost twice the number of neurons throughout their cerebral cortex in comparison to those who developed mental symptoms. It was felt that "those people might have started with a larger brain and more neurons and thus might be said to have a greater reserve."This neurocentric version of reserve relies on a genetically endowed advantage based on increased neuronal numbers.
Another perspective regarding brain reserve involves the concept of "neurocomputational flexibility" wherein certain individuals who have developed a range of cognitive strategies for solving complex problems are more likely to remain normal cognitively for longer despite progression of underlying disease. They may also have a greater number of potential neural pathways for execution of these cognitive processes, thus permitting maintenance of function despite neurological insult. In essence, this suggests that an individual who utilizes a specific brain network more efficiently, or is able to bring alternative brain networks on-line in response to increased demand may thus have greater brain reserve. Such a construct links brain reserve with performance of complex mental activities, increased neural and synaptic (a synapse is the point where one nerve cell contacts another) numbers and consequently enhanced brain function.
Numerous population-based cohort studies have examined the link between complex mental activity and risk of developing dementia. When analyzed together, they revealed an overall risk reduction of 46%. The separate effects of education, occupational complexity and cognitive lifestyle activities were similar in magnitude. The issue is whether such mental activity-related dementia risk remains modifiable in late life. Interestingly, participation in cognitive and social lifestyle activities in later life (independent of either education or occupational experiences) showed significant (50-66%) protection against risk of dementia.
What are the possible mechanisms behind this robust effect? Mental stimulation is a strong stimulator for the generation of a neurochemical called BDNF (Brain-Derived Neurotrophic Factor) and Nerve Growth Factor (NGF). They play critical roles in nerve cell survival, neuronal connectivity, resistance to disease and learning and memory. An enriched mental environment increases generation of new synapses by 150-200%. This effect is especially important for dementing illnesses because of the dramatic loss of synapses in these disorders. Even more intriguing is the suggestion that mental activity may diminish the production of AD neuropathology. These insights are potent incentives to engage in a mentally active lifestyle to ensure a vibrant future life.