COGNITIVE RESERVE

Dr Ravi Soni

Senior Resident

Dept. of Geriatric Mental Health

KGMU

• Why the concept of cognitive reserve?

• Definition

• Theories for explanation

• Passive and active models

• Measures of reserve

• Epidemiological evidences

• Imaging in CR

• Implications of CR for diagnosis, early detection, and treatment of AD

The Concept: Brain Reserve

• There does not seem to be a direct relationship between the degree of brain pathology or damage and the clinical symptoms of that damage.

• Is there a reserve against brain damage?

• For example: Katzman described 10 cases of cognitively normal elderly women who were discovered to have advanced Alzheimer disease (AD) pathology in their brains at death.

Katzman R, Aronson M, Fuld P, et al. Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol. 1989;25:317–324.

Passive Model – Brain Reserve Capacity

• Old concept

• Passive Models - Brain Reserve Capacity (BRC) derives from brain size or neuronal count.

• There may be individual differences in BRC.

• It is fix and does not change with time, experience or training

• There is a critical threshold of BRC: an amount of brain damage sustained before reaching a threshold for clinical expression.

Cognitive Reserve (CR) Model

• The cognitive reserve (CR) model suggests that the brain actively attempts to cope with brain damage by using preexisting cognitive processing approaches or by enlisting compensatory approaches.

• Individuals with more CR would be more successful at coping with the same amount of brain damage.

• provides a ready explanation for why many studies have demonstrated that higher levels of intelligence and of educational and occupational attainment are good predictors of which individuals can sustain greater brain damage before demonstrating functional deficit.

CR – Neural Reserve

• CR may be implemented in 2 forms: neural reserve and neural compensation.

• Neural reserve - brain networks or cognitive paradigms that are less susceptible to disruption, perhaps because they are more efficient or have greater capacity.

• In healthy people – it is used when coping with increased task demands.

• In brain pathology – it could help too…

CR- Neural compensation

• Neural compensation - people suffering from brain pathology use brain structures or networks (and thus cognitive strategies) not normally used by healthy people to compensate for brain damage.

• These concepts are particularly important when attempting to formulate and interpret functional imaging studies that investigate CR.

Models - Summary

• The fact that one patient can maintain more AD pathology than another but appear similar clinically can be explained by the CR models and not by the passive models.

• However, it is likely that both CR concepts are involved in providing reserve against brain damage.

Measures of reserveReserve may be

1. Structural: ‘extra’ neurons and synapses, brain volume, head circumference or dendritic branching

2. Functional: a degree of excess capacity or compensatory mechanisms such that the brain could continue to perform well despite damage

Many of these measures are influenced by life experience and may change over the lifetime.

Question is how to quantify this abstract construct?

• common approach is to use other variables as markers of, or proxies for, reserve; the most common such variable being years of education.

• There are many such variables

Measures of Reserve

• As we discussed, CR (cognitive reserve) is influenced by lifetime experience:

– Measures of socioeconomic status, such as income or occupational attainment.

– Educational attainment including - number of years of formal education, and degree of literacy.

– Measures of various cognitive functions, such as IQ.

Measures of Reserve

• Genetics + Exposure innate intelligence Education (marker of innate intelligence)

• Still, education, or other life experiences, probably impart reserve over and above that obtained from innate intelligence.

• CR is not fixed; at any point in one’s lifetime it results from a combination of exposures.

How does CR affect AD?

• Experiences associated with more CR do not directly affect brain reserve or the development of AD pathology.

• Rather, CR allows some people to better cope with the pathology and remain clinically more intact for longer periods of time.

How does CR affect AD?

• Many of the factors associated with CR may also have direct impact on the brain itself. (ex.-IQ and brain volume).

• Environmental enrichment might prevent or slow accumulation of AD pathology.

• Estimating CR :integrating the interactions between genetics, environmental influences on brain reserve and pathology, and the ability to actively compensate for the effects of pathology.

Epidemiologic Evidence for CR

• Many studies have examined the relation between CR variables and incident dementia.

• Parallel studies have often examined the relation between these variables and cognitive decline in normal aging.

Education and CR

• Several studies in India, England, and the United States reported no association between education and incident dementia.

• However, lower incidence of dementia in subjects with higher education has been reported by at least 8 cohorts, in France, Sweden, Finland, China, and the United States.

Education and CR

• Education has a role in age-related cognitive decline.

• Several studies of normal aging reporting slower cognitive and functional decline in individuals with higher educational attainment.

• The same education related factors that delay the onset of dementia also allow individuals to cope more effectively with brain changes encountered in normal aging.

Occupation and CR

• No or vague association between occupation and incident AD was found.

• Nevertheless, several studies have noted a relationship between occupational attainment and incident dementia.

• Occupational attainment was often noted to interact with educational attainment.

Social Status and CR

• Germany - only poor quality livingaccommodations were associatedwith increased risk of incident dementia.

• Indicators of social isolation such as low frequency of social contacts within and outside the family circle, low standard of social support and living in single person household did not prove to be significant.

Leisure Activities and CR

• Activities associated with lower risk of incident dementia:– Traveling, doing odd jobs, knitting

– Community activities, gardening

– Having an extensive social network, participating in mental, social, and productive activities

– Intellectual activities (reading, playing games, going to classes)

– Leisure activities (reading, playing board games or musical instruments, and dancing)

Life Expectancy and CR

• In a prospective study of AD patients matched for clinical severity at baseline,54 patients with greater education or occupational attainment died sooner than those with less attainment.

• Does this contradict the CR hypothesis?

Life Expectancy and CR

• At any level of clinical severity, the pathology of AD is more advanced in patients with CR.

• At some point, the greater degree of pathology in the high reserve patients would result in more rapid death.

Imaging Studies – resting CBF

• Several imaging studies of CR in AD used resting cerebral blood flow (CBF).

• These studies have found negative correlations between resting CBF and years of education, premorbid IQ, occupation and leisure.

• The negative correlations are consistent with the CR hypothesis’ prediction that at any given level of disease clinical severity a subject with a higher level of CR should have greater AD pathology (ie, lower CBF).

Imaging Studies – resting CBF

Alexander GE, Furey ML, Grady CL, et al. Association of premorbid function with cerebral metabolism in Alzheimer’s disease: implications for the reserve hypothesis. Am J Psychiatr. 1997;154:165–172.

Imaging Studies – resting CBF

Stern Y, Alexander GE, Prohovnik I, et al. Relationship between lifetime occupation and parietal flow: implications for a reserve against Alzheimer’s disease pathology. Neurology. 1995;45:55–60.

Imaging Studies – Neuropathologic

• A neuropathologic analysis showed that for the same degree of brain pathology there was better cognitive function with each year of education.

Bennett DA, Wilson RS, Schneider JA, et al. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology. 2003;60:1909–1915.

Functional Imaging of CR

• Functional imaging studies should be able to capture the differences in how tasks are processed due to CR.

• One approach - to identify patterns of task-related activation that differ between AD patients and controls, and to determine whether they are compensatory.

PET and verbal recognition

• H215O PET was used to measure regional CBF in

patients and healthy elders during a verbal recognition task.

• Task difficulty was adjusted so that each subject’s recognition accuracy was 75%.

• In addition, CBF was measured for different study list size.

PET and verbal recognition

• In healthy elders and 3 AD patients, a network of brain areas was activated during performance:– Left anterior cingulate– Anterior insula– Left basal ganglia

• Higher study list size -> increased recruitment of the network

• Individuals who are able to activate this network to a greater degree may have more reserve against brain damage.

Left anterior cingulate

anterior insula

Basal ganglia

PET and verbal recognition• The remaining 11 AD patients recruited a

different network:– Temporal cortex

– Calcarine cortex

– Posterior cingulate

– Vermis. calcarine

Posterior cingulate

vermis

temporal

Stern Y, Moeller JR, Anderson KE, et al. Different brain networks mediate task performance in normal aging and AD: defining compensation. Neurology. 2000;55:1291–1297.

PET and verbal recognition

• Higher study list size -> increased activation of this network.

• Neural compensation - This alternate network may be used by the AD patients to compensate for the effects of AD pathology.

Neural Compensation

• Is this alternate network associated with better performance?

• In several studies, some elders showed additional activation in areas contralateral to those activated by younger subjects.

• The elders who showed this additional activation performed better than those who did not, indicating that it was compensatory.

PET and Nonverbal Tasks

• A PET study identified brain areas whose activation during performance of a nonverbal memory task correlated with an index of CR calculated from measures of education and literacy.

• Such areas were identified in both healthy controls and patients with AD, suggesting that these areas may reflect the neural instantiation (example) of CR.

PET and Nonverbal Tasks

Scarmeas N, Zarahn E, Anderson KE, et al. Cognitive reserve mediated modulation of positron emission tomographic activations during memory tasks in Alzheimer disease. Arch Neurol. 2004;61: 73–78.

PET and Nonverbal Tasks

• Some brain areas showed:– Increased activation as a function of increased CR

in the elderly controls

– Decreased activation in the AD patients.

• Higher CR -> higher adaptive activation:

Compensation for the effects of AD pathology in the AD patients

• This is consistent with our definition of neural compensation.

Summary

• In summary, the imaging evidence is beginning to provide support for the 2 hypothesized neural mechanisms underlying CR:

• Neural reserve which emphasizes preexisting differences in neural efficiency or capacity.

• Neural compensation, which reflects individual differences in the ability to develop new, compensatory responses to the disabling effects of pathology.

Conclusions

• Clinical observation of mild cognitive impairment may be accompanied by very minimal pathology or more than enough to meet pathologic criteria for AD.

• A proportion of this variability may be explained by CR.

• Measuring CR therefore becomes an important component of the diagnostic process.

Conclusions

• Clinical evaluation alone is an insufficient measure of a patient’s true status.

• Indexes of pathology:– Biomarkers

– Imaging AD pathology itself

– Imaging the effect of pathology on resting metabolism in entire brain

– Imaging the effect of pathology on particularly vulnerable brain area.

Conclusions

• There is a need for measuring individual’s CR - the ability to cope with pathology.

• CR may be evaluated using educational and occupational attainment and quantified using functional imaging.

• The combination of clinical characterization, measures of underlying pathology and indices of CR would provide a more complete picture of a patient’s status.

• Important for: early diagnosis, determine prognoses and progression over time.

Conclusions

• Finally, the fact that different life exposures including education, occupation and leisure, impart reserve against AD in epidemiologic studies raises the possibility that an individual’s CR could be increased through some set of systematic exposures or interventions.

• This would result in a nonpharmacologic approach for reducing risk of developing AD.

How to improve the cognitive reserve?

• Enriched environment(EE)

• Cognitively stimulating activities

• Cognitive training

• Physical training

• likely to increase our CR, thus making us more resilient to cognitive decline and damage

Enriched environment(EE)

• This term has been given to environmental conditions that facilitate enhanced sensory, cognitive, and motor stimulation.

• EE has been seen to improve experience-dependent microdevelopment.

• EE has been found to promote neurogenesis, synaptogenesis, and transgenerational transmission.

• EEs are meaningful social engagement and activities that provide a sense of mastery.

• These are complex, highly structured enjoyable activity that provide opportunity for self-expression, e.g., charity, clubs, group games, voluntary work, and caring for sick.

Cognitively stimulating task

• Sharing knowledge and experiences

• Gardening and other community activities

• Learning magic

• Crossword puzzles

• Juggling

• Formal education, reading books and magazines

• Musical instruments, dancing, and leisure activity

• La Rue recommendation (2008) suggests following for better memory: to carve out time for cognitively stimulating activities that one enjoys, to add some new challenging pursuits as time and energy allow, to engage in these pursuits several times a week, and to participate in social interaction.

Cognitive training• Advanced cognitive training for independent and vital elderly (ACTIVE)

study undertook training of older adults in areas of reasoning, memory, and processing speed.

• Improvement in cognition lasted at least 5 years with booster training.

• In Experience Corps (EC) project, elders were taught literacy, mathematics, and conflict resolution in elementary school. Training showed improvement in executive function and memory.

• There are many cognitive training websites available, few of these include

• www.fitbrains.com

• www.gamesforthebrain.com

• www.mybraintrainer.com

• www.luminosity.com

• www.sharpbrains.com

Physical training

• Aerobic fitness training in older adult promoted significant increase in gray (cortical neurons) and white matter (connecting pathways)

• Physical and cognitive training combined had multiplier effect.

Life course model for better memory

Factors affecting cognitive reserve at various stages ofhuman development

References• Stern Y. Review article: Cognitive Reserve and Alzheimer Disease:

Alzheimer Dis Assoc Disord, Volume 20, Number 2, April–June 2006

• Stern Y. CRITICAL REVIEW: What is cognitive reserve? Theory and research application of the reserve concept. Journal of the International Neuropsychological Society (2002), 8, 448–460

• Prakash J, Ryali V, Srivastava K, Bhat PS, Shashikumar R. Cognitive reserve: The warehouse within. Ind Psychiatry J. 2011 Jul;20(2):79-82.

• Stern Y. Reviews and perspectives: Cognitive reserve. Neuropsychologia 47 (2009) 2015–2028

Thanks