Introduction
Alzheimer’s Disease has been known to humans since 1906, as described by psychiatrist Alois Alzheimer, and gave rise to the concept of cognitive resilience when a discrepancy was observed, that is, some individuals have unaffected cognitive abilities despite the presence of AD pathology. AD is characterized by changes in memory, thinking, and behavior, but this resilience of the mind protects an individual’s cognition from these negative effects despite the presence of significant AD pathology. The impactful role of resilience capacity lies in the fact that those with lower resilience have higher chances of cognitive decline due to amyloid (abnormal protein deposition). While everyone has some degree of cognitive resilience, it varies from person to person based on their genes.
What about biology?
To give a brief on the biology of AD, it is a neurodegenerative disorder caused by deposition of protein in the brain nerve cells (amyloid plaques), or abnormal accumulation of hyperphosphorylated tau in neurons (neurofibrillary tangles or NFTs), dystrophic neurites, and shrinking of neurons and brain regions. These abnormal alterations cause cognitive decline and behavioral changes. On the other hand, the biology of cognitive resilience has been a recent topic of research, a study has identified eight proteins from the the human dorsolateral prefrontal cortex namely NRN1, ACTN4, EPHX4, RPH3A, SGTB, CPLX1, and SH3GL1(higher level) and of UBA1 (lower level) are associated with greater resilience and slower cognitive decline. Not only the proteins but also a cell organelle, mitochondria, and their neuronal activity play a role in cognitive stability with or without the burden of brain pathologies.
What determines cognitive resilience?
You might have heard of cognitive reserve, a concept that often overlaps with cognitive resilience, as the two distinct components of the brain work hand-in-hand. Measuring cognitive reserve is a great way to measure cognitive resilience as cognitive reserve is a latent variable that uses different brain networks and maximizes cognitive performance to compensate for the harm done by AD pathology and cognitive resilience maintains cognitive abilities despite the presence of AD pathology.
While cognitive resilience has its own weaknesses in the form of brain pathologies (like pure AD, cerebral infarctions and Parkinson’s Disease) and psychosocial factors (such as chronic distress, loneliness, neuroticism, and depression) that degrade resilience, at the same time some psychosocial factors (high conscientiousness) can modify resilience by reducing the negative effect of pathology on cognition.
Individuals with low BMI have higher resilience, and this study talks about the positive impact of short-term smoking on cognitive resilience. They hypothesize that due to its cholinomimetic nature, nicotine brings forth a neuroprotective effect. A protective barrier against AD is Education, as higher education results in more effective use of brain networks, therefore supporting cognitive resilience. Furthermore, early writing skills and high idea density are found to increase cognitive resilience. In fact, the difference in cognitive resilience between different genders and sexes has reduced with the increase in educational opportunities for women. Furthermore, a cross-sectional study supports that female sex, younger age, cortical thickness, and higher education are positively associated with greater resilience.
An intergenerational study suggests that race, ethnicity, and linguistic abilities influence cognitive resilience as individuals in middle age, whose parents have dementia, demonstrated poorer cognitive functioning. This impact of parental history of AD on poor cognitive abilities is determined by race, ethnicity, and linguistic abilities. Based on race, a study states that predictors of cognitive resilience differ among white APOE ε4 carriers and black APOE ε4 carriers. For the white APOE ε4 carriers, the predictors include absence of recent negative life events, a higher literacy and educational level, advanced age, and time spent reading. Whereas the predictors of cognitive resilience in black APOE ε4 carriers, a higher literacy and educational level, female sex, and the absence of diabetes mellitus.
This is supported by another study stating that those who spoke four or more languages had higher cognitive resilience than bilinguals, and even states that speaking German has no such significant influence on cognitive resilience. A neuropathological evaluation of the Honolulu-Asia Aging Study (HAAS) and the Nun Study states that sex, ethnicity, and lifestyle factors have a significant association with resistance and the development of brain pathologies with age.
Conclusion
Cognitive Resilience is the resilience towards the negative effects of AD pathology on cognition. Cognitive resilience depends on certain proteins and enrichment of the mitochondria. It is determined by various factors like cognitive reserve, race, ethnicity, early writing skills, linguistic abilities, gender/sex, educational level, parental history of dementia/ AD pathology, psychosocial factors such as social connectedness, neuroticism, conscientiousness, and depression. Cognitive resilience provides a great scope of research, ranging from understanding the impact of various factors on cognitive resilience to the biological basis of cognitive resilience.
Heet Suthar
