Unraveling the mystery of cognitive reserve.

ABSTRACT

In 1913, no less than Santiago Ramon y Cajal, pioneer of the neuron doctrine, wrote, ‘In the adult brain, nervous pathways are fixed and immutable; everything may die, nothing may be regenerated’ (Cajal 1913/1959, p 750). This stagnant view of the brain lingered in neurology for several decades, and was regularly provided as an explanation when a patient’s recovery from a stroke or brain injury was minimal or elusive. Our current understanding, however, is radically and very importantly different. The human brain – even the adult human brain – is, in fact, remarkably plastic. This enduring neuroplasticity is fundamental to the brain’s mechanisms for coping with disease and injury. As the world’s population ages, this is becoming increasingly evident. The question now emerging in the field, however, lies not in the ubiquity of agerelated disorders such as Alzheimer’s disease (AD), but in the individual variability of their onset. Alzheimer’s can now be diagnosed with reasonable consistency several academic centres report up to 90% correlation between clinical diagnoses and autopsy diagnoses of AD (Cummings et al. 1998). However, the relationship between the severity of clinical symptoms and observable neuropathology is far from direct. This was particularly brought to light in 1989, when Katzman et al. performed postmortem analyses of the brains of 137 nursing home patients. The patients’ cognitive abilities had been monitored at the nursing home, and these records were compared with the neuropathology observed during dissection. They unexpectedly found that the brains of 10 of the subjects, who had been assessed as having unimpaired cognitive function throughout their lives, in fact displayed neuropathology that surpassed the criteria for diagnosis of AD. These individuals also happened to have heavier and more neuron-dense brains than controls, which they concluded must have afforded some ‘reserve’ that prevented the symptoms of the disease from manifesting. There are two primary theories that attempt to explain such a discrepancy. Brain reserve (BR) refers to tangible individual differences such as brain size and dendritic density, as was noticed by Katzman et al. (1989), BR is considered a passive ‘threshold’ model of reserve once a certain threshold for brain damage is exceeded, symptoms of cognitive decline begin to manifest. Cognitive reserve (CR), on the other hand, is considered an active model the brain attempts to compensate for cognitive damage by implementing alternate mechanisms in place of the damaged networks. A brain that has engaged in activities that enhance this cognitive flexibility is therefore better equipped to cope with damage than one that has not (Stern, 2002). Barulli and Stern (2013) argue that these theories are complementary rather than competing. Like any complex human trait, resilience against brain damage appears to be constructed of a cocktail of genetics, environment and experience. The greater the resolution with which brain structures can be visualized and molecular pathways leading to plasticity are understood, the more the two theories are liable to overlap. Nevertheless, it remains that the environmental component can be manipulated to favour reserve. As a result, much of the current literature concerning reserve focuses on identifying lifestyle factors that may improve CR. Higher level of education, occupational complexity and physical and intellectual leisure activities have all been found to consistently correlate with increased CR (Verghese et al. 2003; Potter et al. 2008; Valenzuela and Sachdev 2009). Recently, bilingualism as a CR-improving factor has received much attention. The original studies in this area found a highly significant effect of lifelong bilingualism on the onset of AD, and are textbook examples of CR in effect. The first, by Craik, Bialystok and Freedman (2010), retrospectively analysed the medical records of 211 elderly Canadians diagnosed with AD. The records contained detailed language histories, based on which 102 were classified as bilingual and 109 as monolingual. On comparison, the bilingual group showed an onset of AD symptoms on average 5.1 years