Task 8. Successful ageing
Task 8. Successful ageing
Studied to explain for differences between individuals in suceptibility to age-related brain changes and pathology.
Reserve acts as a moderator between pathology and clinical outcome, accounting for the discontinuity.
2 way of understanding reserve
originally quantitative. Number of neurons or synapse available to be lost. A larger brain my simply tolerate more pathology before it reaches a critical threshold for clinical symptoms to appear. Nowadays more underlying biological features are suggested: stimulating environments associated with neurogenesis and upregulation of BDNF, which fosters neural plasticity and could impart reserve
: active form of reserve in which brain function rather than brain size is the relevant variable. The brain actively attempts to cope with pathology by using pre-existing cognitive-processing approaches or compensatory mechanisms. An individual with higher cognitive reserve would cope better with the same amount of pathology that one with low cognitive reserve (independently of brain sizes).
Both make independent and synergistic contributions to understanding of individual differences in resilience to brain pathology.
People with greater reserve should be able to tolerate more AD pathology - the onset of clinical dementia in these individuals should be delayed.
Education and occupational (low or high positions) experiences created a reserve against the effect of AD pathology.
Also, people engaged in more leisure activities had a lower risk of developing dementia.
Neuroimaging studies of cognitive reserve
Resting regional cerebral blood flow
Higher level of education was associated with greater depletion of blood flow in the parieto-temporal area, where PET changes are seen in patients with AD.
An inverse relation was found between resting regional cerebral blood flow and years of education
Patients with higher cognitive reserve had more AD pathology than those with lower cognitive reserve even though they appeared clinically similar
(showed less clinical manifestations even if they were more affected).
: The cognitive or neural mechanisms that might underlie the reserve against age-related or AD pathology are unknown
idea that cognitive reserve could be associated with differences between individuals in the resilience of pre-existing cognitive networks.
=> Cognitive reserve might be mediated by the same networks that are used by individuals in the absence of pathology related to age or disease. Efficiency of networks reduce with age. Individuals with more efficient or higher-capacity networks could have more resilience in the face of age-related or disease-related changes.
idea that some individuals might be better than others at using compensatory mechanisms.
Assesed by imaging studies
: What they showed is that two networks of brain regions seemed to work together as the task got harder (increased FMRI signal). The first network was used by both the young and elderly adults and involved areas often associated with WM. The second network was primarily characterised by activation in parahippocampal areas and was used consistently only in the elderly group.
The elderly adults that used that network the most had the worst performance.
This finding show neural compensation, how age-related changes limit the efficiency of the first network, so the second one is increasingly used. These people can still do the task, but not as good as the ones that used just the first network.
Individuals with high cognitive reserve
atrophy in the first network and still preserve performance without having to resort to using the second network. Patients with high cognitive reserve can make use of resources that are separate from those directly involved in task performance.
What is Successful Ageing?
Rowe & Kahn
: Proposed a distinction between usual and successful ageing as apposed to the classical between normal and pathological.
: in the absence of disease and disability, other age-related alterations in physical function and cognitive were normal, determined by intrinsic aging processes, primarily genetic, and not associated with risk (implicit assumption of early gerontologist)
3 main components:
. It is the combination of the absence of disease, maintenance of functional capacities and an active life that represent fully the concept.
High cognitive and physical functional capacity
Predictors of decline in physical performance
: less income, higher BMI, greater fat, high blood pressure, lower initial cognitive performance
Maintenance of high physical performance
. moderate and/or strenuous leisure activity and emotional support from family and friends. Moderate levels of exercise have also advantages.
people´s beliefs in their capabilities to organize and execute the courses of action required to deal with prospective situations. It influences persistence in solving cognitive problems.
Plasticity is still possible and cognitive training.
Education was the strongest predictor
, and considered a major protective factor against decrease in cog functions. Two effects: direct beneficial effect of education early in life on brain circuitry and function, and possibility that education is a proxy for life-long intellectual abilities.
Active engagement in life
(creates social value)
established predictor of sustained productive behaviour, paid and unpaid. Establish habits and values that express themselves in later life as a higher functional status and engagement in productive behaviour.
mastery and control are predictors of sustained activity.
men and women high in cog and physical function are 3 times more likely to be doing paid work and volunteer work.
response to stress:
Ability of people with successful aging to move in and out of success. Most older people have experience stressful life events. Concept of resilience to describe the rapidity and completeness with which people recover from such episodes and return to meeting the criteria of success.
(contacts and transactions with others, exchange of information, emotional support and direct activity). Being part of a social network is a significant determinan for longevity (esp.men).
socio- emotional support
(expression of affection, respect and the like) and
l (direct assistance, such as giving physical help, doing chores, providing transportation or giving money)
effectiveness of the support depend on how appropriate the supportive acts are for a specific situation or person.
Isolation and lack of social interest
Low probability of disease and disease-related dissability
Absence or presence of disease itself
Absence, presence or severity of risk factors for disease
:The population at lowest risk are the one with successfull ageing, because with time, risk factors increase and aged population is very vulnerable.
Hereditability and life-style
: Increased risk of disability with advancing age was considered to result from an intrinsic and inevitable aging process. However, many usual characteristics are due to lifestyle and other factors that may be
age-related (they increase with age), but not age dependent (caused by age itself)
Importance of life-style factors:
some chronic disease, are age-related factors but potentially avoidable factors, such as reduced physical activity and dietary factors.
(2) With advancing age the relative contribution of genetic factors decreases and the force of non-genetic factors increases.
(3) usual aging characteristics are modifiable
(1) Intrinsic factors alone do not dominate the determination of risk in advancing age. Extrinsic environmental factors, including lifestly, play an important role.
importance of environmental and behavioural factors in determining the risk of disease in later life.
Linguistic ability in early life and Longevity: findings from Nun Study. Snowdown
Threshold model of dementia:
individuals will exhibit dementia only if their cognitive or neurological reserve capacity falls below a specific threshold (e.g. a critical volume of functional brain tissue)- neurocognitive reserve developed in early life may buffer elderly individuals from the consequence of dementia.
: low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Concluded that low linguistic ability in early life was a strong predictor of poor cognitive function and AD in late life
Low idea density in early life was present in most cases with AD, compared with a much lower rate in nuns without AD. Also, those with low idea density had more neuropathological evidence of AD.
Grammatical complexity: weak negative association with neuropathology confirmed AD and with neurofibrillary tangles in the hippocampus and neocortex
The findings support a strong relationship between cognitive ability in early life, as indicated by linguist ability and cognitive function, and AD in later life. Low idea density in autobiographies written at 22, increased risk of poor cognitive function and AD 58 years later
Sisters with low linguistic ability in early life, may have less neurocognitive reserve capacity
when they entered the convent. This could make them more vulnerable to consequences of AD.
After examining the data, they
postulated that low linguistic ability in early life may be an early expression of AD disease neuropathology.
Expected that high linguistic ability would prevent those with abundant tangles and senile plaques from expressing the symptoms. Only one sister met the pathologic criteria but did not show intellectual decline consistent with dementia
determine if linguist ability in early life is associated with cognitive function and AD in later life.
Education may reflect cognitive ability and availability of neurocognitive reserve in later life. Linguistic ability in early life may a better marker than education of important aspects of cognitive ability, neurocognitive development, and neurologic reserve in early life => a high level of linguistic ability may buffer elderly individuals from consequence of dementia.
Assessed linguistic abilities
:measures of linguistic abilities derived from autobiographies written at a mean age of 22 years. By analysing the form and content of oral and written language samples to revel how normal aging and the progression of AD affect linguistic ability. Working memory limitations can lead to decline in grammatical complexity and density of ideas in older adults.
educational level, vocabulary and general knowledge. Defined as the average number of ideas expressed per 10 words: elementary propositions, typically a verb, adjective adverb or prepositional phrase. Complex propositions that stated or inferred causal, temporal, or other relationships between ideas also were counted.
: working memory, performance on speeded tasks, and writing skills. Computed using the Developmental level metric modified by Cheung and Kemper. It classifies sentences according to eight levels of grammatical complexity (from 0 -simple one-clause sentence- to seven -complex sentences with multiple forms of embedding and subordination).
New handwritten autobiographies were elicited. And both autobiographies (original and new one) highly correlated for idea density and grammatical complexity.
Sister Mary´s Profile
Professional life: A 19 she took the religious vows. Also, she began to teach seventh and eighth grades. She taught full time until she was 77 years old. Worked part time as a math teacher for several years after retiring. Very active in the community and interested about world events. Avid reader.
678 school sister of Notre Dame that participate in annual assessment of cognitive and physical function, and donate their brains at death for neuropathologic studies.
Last assessment: average age of 85 years of participants and 31% cognitive impaired. Sister Mary was 101 year old and cognitively intact during her last functional assessment.
Sister Mary´s case
is the gold standard for successful cognitive ageing.
her brain contained abundant neurofibrillary tangles and senile plaques, the classic neuropathologic lesions of Alzheimer´s disease
Battery of neuropsychological tests in the study:
eight tests that assess memory, concentration, language, visuospatial ability, and orientation to time and place. :
Results of her last evaluation:
Sister Mary received a MMSE score of 27, within the normal range. This is remarkable because: she was 101 years of age, had less formal education than the other sisters.
When considering her old age and education in a regression analysis, she did substantially better on each of the eight tests than the other sister. The MMSE, for example, was well above the 4 that was predicted based on her low age and low education.
Sister Mary´s cognitive function was stable and did not visibly change during most of the 10 years.
Nevertheless, it was reported that before her death she became quieter and less energetic. Sisters who were with her at the time of her death indicated that her mind was clear until the end.
several medical problems,
such as heart disease and other chronic diseases, that are normally associated with diminished cognitive functions. Also, very low body weight and significant weight loss have moderately strong associations with cognitive functions tests.
(comparison to the sister´s)
Diffuse plaques in the hippocampus and neocortex
No infarcts, but focal atherosclerotic deposits in the middle brain, internal carotid, and vertebral arteries.
Sisters with brain infarctions or with brains weight less than 1,000 grams also showed significantly lower performance on the cognitive tests than did sisters without these conditions.
fewer neurofibrillary tangles and neuritic plaques in the neocortex.
Neurofibrillary tangles in the neocortex had strong associations with poor performance on each of the eight cognitive function test. Diffuse plaques in the hippocampus and neocortex had weak and inconsistent associations with performance on the eight cognitive tests.
Low brain weight. Moderate degree of frontal, parietal, and temporal lobe atrophy.
==> Given these relationships, sister Mary mat have
* maintained relatively high cognitive functions during old age because of the type and location of her AD lesions and the absence of brain infarcts.
Although she had high number of neurofibrillary tangles in her brain, very few were present in the neocortex, lack of significant lesions in association area´s. High number of diffuse plaques and hippocampus and neocortex also may reflect a less sever form of AD.
Sister Mary had enough neocortical senile plaques to meet the
Khachaturian criterian for AD,
but not enough neocortial neuritic plaques to meet the CERAD criteria. o It is arguable if she had the type and quantity lesions that are necessary to meet the neuropathologic criteria for AD. Her lesions still may have caused damage to the brain and reduced her cognitive abilities, but not enough to cause AD.
Cognitive impairment not an inevitable cause of aging and disease
Active life and taught until her death
She presented several AD lesions and many health problems: weight loss, numerous chronic diseases and AD lesions would be expected to affect cognition. But she appeared to be cognitively intact, with good short-term memory and excellent orientation.
Sister Mary may have entered older age with superior cognitive ability and as the neuropathology of AD spread in her brain, slipped from a superior to a very good level of cognitive performance, without dropping to a functional level typical of someone with dementia (less severe form of the disease)
Lack of brain infarcts and the small number of neurofibrillary tangles in neocortex may have protected her from the loss of cognitive abilities
8 years of formal education
=> she took summer courses within 22 years and got a high school diploma at 41. She maintained an A average.