The puzzle of preserved cognition in the oldest old.

Although epidemiological studies predict an exponential increase in the prevalence of dementia with age, recent studies have demonstrated that the oldest old are actually less frequently affected by dementia than the younger elderly. To explain this, I suggest a parallel between brain ageing and Alzheimer's disease (AD) and assume that theories concerning the brain's vulnerability to AD and its individual variability may also explain why some of the oldest old remain cognitively efficient. Some theories argue that AD is due to the continuing presence of the immature neurones vulnerable to amyloid beta protein (Aß) that are normally involved in brain development and then removed as a result of cell selection by the proteins associated with both brain development and AD. If a dysfunction in cell selection allows these immature neurones to survive, they degenerate early as a result of the neurotoxic action of Aß accumulation, which their mature counterparts can withstand. Consequently, age at the time of onset of AD and its clinical presentations depend on the number and location of such immature cells. I speculate that the same mechanism is responsible for the variability of normal brain ageing: the oldest old with well-preserved cognitive function are people genetically programmed for extreme ageing who have benefited from better cell selection during prenatal and neonatal life and therefore have fewer surviving neurones vulnerable to amyloid-promoted degeneration, whereas the process of early life cell selection was less successful in the oldest old who develop dementia.