Behaviour and life experience can alter the trajectory of the decline of brain function

Question 1

Over the past two centuries human life expectancy has more than X in the developed world. Says who?

Answer 1

doubled

Oeppen & Vaupel, 2002

Question 2

What did Oeppen and Vaupel 2002 find?

Answer 2

That over the past two centuries human life expectancy has more than doubled in the developed world.

Question 3

Over the past two centuries human life expectancy has more than doubled in the developed world (Oeppen & Vaupel, 2002) - what has this resulted in?

Answer 3

a dramatic increase in the number of older individuals

Question 4

Advancing age is associated with what?

Answer 4

declines in function which ultimately lead to a loss of independence accompanied by increased prevalence of age associated diseases and frailty (Doherty, 2003).

Question 5

Indeed, healthy life expectancy, termed [blank], is not keeping pace with average life expectancy - says who?

Answer 5

‘the healthspan’

House of Lord Science and Technology Committee, 2005

Question 6

Indeed, healthy life expectancy, termed ‘the healthspan’, is not keeping pace with average life expectancy (House of Lord Science and Technology Committee, 2005), such that …

Answer 6

the years spent with poor health and disabilities in old age are increasing.

Question 7

What was the term coined by the House of Lords Science and Technology Committee, 2005?

Answer 7

‘healthspan’ - used to describe healthy life expectancy

Question 8

the years spent with poor health and disabilities in old age are increasing. However…

Answer 8

there are substantial individual differences in the trajectory of the decline of brain function

Question 9

However, there are substantial individual differences in the trajectory of the decline of brain function; and these are …

Answer 9

becoming of increasing interest in the drive to find strategies by which healthspan can be increased, and the trajectory of cognitive aging and arrival at frailty slowed down.

Question 10

Structure of intro? 5 points

Answer 10

1. human life expectancy doubled - more old people
2. This associated with decline in function
3. Healthspan not keeping pace
4. substantial individual differences
5. These becoming of interest

Question 11

Essay structure for decline of brain function? 6 pts

Answer 11

1. Intro
2. Structure
3. Define cognitive aging
4. challenges towards defining and understanding it
5. Influencers to cognitive decline (diet; physical activity; mental activity)
6. conclusion

Question 12

What is cognitive aging?

Answer 12

Cognitive aging is a term that describes a process of gradual, longitudinal changes in cognitive functions that accompany the aging process.

Question 13

Is the trajectory of cognitive the same across all cognitive functions?

Answer 13

The trajectory of cognitive change varies for different cognitive functions; there is little age-associated decline in some mental functions (such as verbal ability, some numerical abilities, and general knowledge), but other mental capabilities decline from middle age onwards, or even earlier. The latter include aspects of memory, executive functions, processing speeds and reasoning.

Question 14

Which mental functions do not experience much cognitive decline?

Answer 14

verbal ability; some numerical abilities; general knowledge

Question 15

Which mental functions decline from middle age onwards?

Answer 15

memory; executive functions; processing speeds and reasoning

Question 16

Challenges to Understanding Cognitive Aging

Firstly, it is important to note that here we will focus, as much as possible, on ‘normative cognitive aging’ - why?

Answer 16

this is because the dementias are not only quantitatively different in the degree of cognitive decline, but they are often qualitatively different in the pattern of decline across the various cognitive abilities

Question 17

the dementias are not only quantitatively different in the degree of cognitive decline, but they are often qualitatively different in the pattern of decline across the various cognitive abilities. For example …

Answer 17

Alzeimer’s disease is characterized by marked impairment of episodic memory and frontotemporal dementia by impaired executive function.

Question 18

Alzeimer’s disease is characterized by marked impairment of episodic memory and frontotemporal dementia by impaired executive function. Moreover…

Answer 18

people with dementia often exhibit changes in behavior

Question 19

However, it is notable that there are problems in distinguishing between non-normative and normative cognitive aging; this is partially because …

Answer 19

neuropathological changes of Alzheimer’s disease are widespread in older people’s brains

Question 20

it is notable that there are problems in distinguishing between non-normative and normative cognitive aging; this is partially because neuropathological changes of Alzheimer’s disease are widespread in older people’s brains. Indeed, …

Answer 20

in the MRC Cognitive Function in Aging Study (CFAS), around one-third of participants without dementia had moderate or severe neuritic plaque scores at autopsy (MRC CFAS, 2001).

Question 21

What was found in the MRC Cognitive Function in Aging Study (CFAS) 2001?

Answer 21

That around one-third of participants without dementia had moderate or severe neuritic plaque scores at autopsy

Question 22

Who found That around one-third of participants without dementia had moderate or severe neuritic plaque scores at autopsy?

Answer 22

The MRC Cognitive Function in Aging Study (CFAS) 2001

Question 23

Another problem has been recognized that impacts upon our understanding of the relationship between physical health and age-associated cognitive decline - what is it?

Answer 23

several disease states thought to affect cognition adversely are more common in people with lower early life IQ

Question 24

Another problem has been recognized that impacts upon our understanding of the relationship between physical health and age-associated cognitive decline: several disease states thought to affect cognition adversely are more common in people with lower early life IQ - why is this a problem?

Answer 24

Since childhood IQ is itself a strong predictor of cognitive abilities later in life, the disease state may be acting as a marker of lower childhood IQ, and this might explain some of the association with lower cognitive abilities in old age.

Question 25

Since childhood IQ is itself a strong predictor of cognitive abilities later in life, the disease state may be acting as a marker of lower childhood IQ, and this might explain some of the association with lower cognitive abilities in old age. For example…

Answer 25

lower childhood IQ is associated with elevated blood pressure in middle age even after adjustment for social class, smoking and other factors (Starr et al., 2004).

Question 26

Who found that lower childhood IQ is associated with elevated blood pressure in middle age even after adjustment for social class, smoking and other factors?

Answer 26

Starr et al 2004

Question 27

What did Starr et al 2004 found?

Answer 27

That lower childhood IQ is associated with elevated blood pressure in middle age, even after adjustment for social class, smoking and other factors

Question 28

High blood pressure is thought to lead to cognitive decline but few studies that examine this relationship adjust for what?

Answer 28

the contribution made by childhood IQ to cognition in later adult life.

Question 29

High blood pressure is thought to lead to cognitive decline but few studies that examine this relationship adjust for the contribution made by childhood IQ to cognition in later adult life. Hence, age-associated cognitive decline is best considered in terms of what?

Answer 29

a lifecourse perspective

Question 30

Hence, age-associated cognitive decline is best considered in terms of a lifecourse perspective. - what does this mean?

Answer 30

What appears to be the effect of an illness state on cognitive ability in old age, might be in part the reverse: the effect of early life cognition on the risk of developing the disease state.

Question 31

Influencers to Cognitive Decline

What are we going to examine in this section?

Answer 31

We are now going to examine the evidence that diet, physical activity and mental activity can influence the rate of cognitive decline.

Question 32

Diet

The role of diet in successful brain ageing has been attracting increasing scientific and public interest. - why?

Answer 32

Recent findings suggest that improving the diet of older people might help to delay the onset, or slow the progression, of age-associated cognitive decline.

Question 33

Dietary Fatty Acids.

Who examined the association between intake of linoleic PUFAs and fish consumption and subsequent cognitive decline?

Answer 33

Kalmijn et al (1997)

Question 34

What are PUFAs

Answer 34

Polyunsaturated fatty acids

Question 35

What did Kalmujn and colleagues (1997) examine?

Answer 35

the association between intake of linoleic PUFAs and fish consumption and subsequent cognitive decline

Question 36

Kalmujn and colleagues (1997) conducted a study examining the association between intake of linoleic PUFAs and fish consumption and subsequent cognitive decline - what kind of a study was it? From what was it based? What was the sample?

Answer 36

A population based study from the Zutphen Elderly Study

476 men aged 69-89 years

Question 37

Kalmujn and colleagues (1997) conducted a study examining the association between intake of linoleic PUFAs and fish consumption and subsequent cognitive decline - what did they find?

Answer 37

Higher rates of linoleic PUFAs and fish consumption were shown to protect against incident cognitive impairment and cognitive declined, defined by performance on the MMSE

Question 38

What did Kalmujn and colleagues (1997) do that strengthened their study?

Answer 38

They controlled other confounding dietary elements

Question 39

Similarly to Kalmujn and colleagues (1997), what did van Gelder and colleagues (2007) find? 2 pts

Answer 39

that elderly men who consumed greater amounts of fish were significantly less likely to exhibit cognitive decline relative to men who did not consume fish

In addition, greater fish consumption seemed to protect against cognitive decline in a dose response fashion.

Question 40

Who found that elderly men who consumed greater amounts of fish were significantly less likely to exhibit cognitive decline relative to men who did not consume fish. ? what else did they find?

Answer 40

van Gelder and colleagues (2007)

In addition, greater fish consumption seemed to protect against cognitive decline in a dose response fashion.

Question 41

Antioxidants, Fruits, and Vegetables.

What is greater antioxidant intake hypothesised to prevent?

Answer 41

age-related neurologic dysfunction

Question 42

Why is greater antioxidant intake hypothesised to prevent age related neurologic dysfunction?

Answer 42

because brain tissue contains low levels of endogenous antioxidants and is therefore particularly vulnerable to free-radical damage

Question 43

Moreover, oxidative stress has been implicated as what?

Answer 43

one of the primary mechanisms of age-related neuronal decline

Question 44

Greater antioxidant intake is hypothesized to prevent age-related neurologic dysfunction because brain tissue contains low levels of endogenous antioxidants and is therefore particularly vulnerable to free-radical damage. Moreover, oxidative stress has been implicated as one of the primary mechanisms of age-related neuronal decline. Accordingly…

Answer 44

there has been great interest in the role of antioxidants in the prevention of age-related cognitive decline.

Question 45

Why has there been great interest in the role of antioxidants in the prevention of age-related cognitive decline?

Answer 45

1. Greater antioxidant intake is hypothesized to prevent age-related neurologic dysfunction because brain tissue contains low levels of endogenous antioxidants and is therefore particularly vulnerable to free-radical damage
2. oxidative stress has been implicated as one of the primary mechanisms of age-related neuronal decline

Question 46

Early studies of antioxidants emerged from what?

Answer 46

uncontrolled observation studies in which greater consumptions of fruits and vegetables were shown to be associated with better cognitive function`

Question 47

Early studies of antioxidants emerged from uncontrolled observation studies in which greater consumptions of fruits and vegetables were shown to be associated with better cognitive function. For example?

Answer 47

Ortega and colleague (1997)demonstrated that high intakes of fruit, folate, carbohydrate thiamine, and vitamin C were associated with reduced rates of cognitive impairment among 260 individuals aged 65-90 years

Question 48

Who extended Ortega and colleague’s findings?

Answer 48

Morris and colleagues (2006)

Question 49

Morris and colleagues (2006) extended these findings - noting what?

Answer 49

that greater intake of vegetables, but not fruits, was associated with improved cognitive performance among 3717 older adults participating in the Chicago Health and Aging study.

Question 50

Although this research is promising, what do we need to remember?

Answer 50

the interaction between genes and nutrition in recent research highlights the interplay between internal and external environments.

Question 51

Although this research is promising, the interaction between genes and nutrition in recent research highlights the interplay between internal and external environments. For example?

Answer 51

Cognitive benefits were found in older adults consuming omega-3 fatty acids, but only in non-APOE e4 carriers (Whalley, Deary and Starr, 2008).

Question 52

Cognitive benefits were found in older adults consuming omega-3 fatty acids, but only in non-APOE e4 carriers (Whalley, Deary and Starr, 2008). What does this finding support?

Answer 52

the concept of an individual response to dietary intake and heterogeneity in cognitive ageing.

Question 53

Physical Activity

When considering potential determinants of age-associated cognitive decline, engaged and active lifestyles are often reported as what?

Answer 53

protective

Question 54

When considering potential determinants of age-associated cognitive decline, engaged and active lifestyles are often reported as protective. A recent UK Government review incorporated research linking what? Full citation?

Answer 54

physical activity or exercise and cognitive function, the consensus being that age-associated cognitive decline is delayed or reduced in more physically active individuals

(Foresight Mental Capital and Wellbeing Project, 2008).

Question 55

What further investigation is warranted in relation to physical activity and cognitive decline?

Answer 55

to examine whether there are critical periods across the lifespan when physical activity needs to initiated and maintained

Question 56

Additionally, not all studies report an exercise-cognitive decline association. Why might this be? 3 pts

Answer 56

perhaps due to:

the variability in the physical activity measurements,

the validity of the cognitive assessments and length of follow-up in old age,

the timing and duration of the physical activity itself

(Fratiglioni et al. 2004)

Question 57

That said, there are a number of mechanistic hypotheses which could account for an association between increased physical activity and reduced cognitive decline. Most notably what?

Answer 57

cardiovascular risk and disease profiles are known to play a role in the trajectory of cognitive decline in later life; physical activity lowers these risk factors ( Fratiglioni et al. 2004).

Question 58

Mental Activity

In this domain, the notion of ‘[blank]’ is proposed

Answer 58

use it or lose it

Question 59

In this domain, the notion of ‘use it or lose it’ is proposed: - elaborate?

Answer 59

the continued deployment of cognitive abilities through activities requiring cognitive effort may have direct effects on the brain, in terms of structure and/or function.

Question 60

In this domain, the notion of ‘use it or lose it’ is proposed: the continued deployment of cognitive abilities through activities requiring cognitive effort may have direct effects on the brain, in terms of structure and/or function. For example ?

Answer 60

Hultsch and colleagues (1999) examined the relationship between an engaged lifestyle, as defined by participation in a variety of intellectually challenging activities and cognition.

High levels of participation in activities associated with an engaged lifestyle, and particularly novel information-processing activities were associated with higher levels of cognitive function over a 6 year period.

Question 61

What did Hultsch and colleagues 1999 examine?

Answer 61

the relationship between an engaged lifestyle, as defined by participation in a variety of intellectually challenging activities and cognition.

Question 62

Who examined the relationship between an engaged lifestyle, as defined by participation in a variety of intellectually challenging activities and cognition?

Answer 62

Hultsch and colleagues (1999)

Question 63

When Hultsch and colleagues (1999) examined the relationship between an engaged lifestyle and cognition, what did they find?

Answer 63

High levels of participation in activities associated with an engaged lifestyle, and particularly novel information-processing activities were associated with higher levels of cognitive function over a 6 year period.

Question 64

What is one confound to Hultsch et al (1999) study examining the relationship between an engaged lifestyle and cognition?

Answer 64

That the directionality of the relationship, over the six year period, between engagement in novel activities and cognitive vitality was ambiguous.

Question 65

The notion of use it or lose it is closely related to what hypothesis?

Answer 65

the cognitive reserve hypothesis

Question 66

What does the cognitive reserve hypothesis state?

Answer 66

Individuals who are more cognitively active or engaged may accrue greater ‘reserve capacity’ across the lifecourse, and subsequently delay the onset of age-associated cognitive decline or reduce the impact of this.

Question 67

What did Pushkar and colleagues (1999) suggest in relation to Hultsch et al’s (1999) study?

Answer 67

that the ambiguous and somewhat modest relationship between lifestyle engagement and cognitive function may be due, in part, to the high mean level of education of the participants (44% had more than 14 years, and 83% at least 11 years).

Question 68

It is conceivable that an engaged lifestyle may have a larger influence on the cognitive vitality of an educationally [blank] group of adults.

Answer 68

heterogeneous

Question 69

It is conceivable that an engaged lifestyle may have a larger influence on the cognitive vitality of an educationally heterogeneous group of adults. Indeed, this proposal is consistent with the results of a study conducted by who? what did they find?

Answer 69

Christensen and colleagues (1997) in which the relationship between mental engagement and cognitive change over a 5 year period was stronger for blue-collar workers than elite academics.

Question 70

Further, any association found between mentally stimulating activities and cognitive decline must be clearly shown to be independent of what?

Answer 70

premorbid cognitive function

Question 71

Further, any association found between mentally stimulating activities and cognitive decline must be clearly shown to be independent of premorbid cognitive function. What does this mean?

Answer 71

That is, the association must not be driven by the fact that higher ability individuals are more likely to be cognitively active throughout life and into old age (not just in terms of leisure, but occupationally also); another example of possible reverse causation.

Question 72

the association must not be driven by the fact that higher ability individuals are more likely to be cognitively active throughout life and into old age (not just in terms of leisure, but occupationally also); another example of possible reverse causation. If it is what might the effect be due to?

Answer 72

The presumed protective effect may be due to the high degree of stability in cognitive function across the lifespan and not from participation in the activities themselves.

Question 73

To examine if there is truly a protective effect, what is needed?

Answer 73

more studies are needed which are able to control for an early measure of premorbid cognitive function.

Question 74

Such activities may suggest simple, cost-effective lifestyle interventions to ameliorate or delay age-associated cognitive decline. However…

Answer 74

to-date cognitive intervention trials have not produced robust replicable benefits.

Question 75

A recent review by Papp and colleagues (2009) including 10 randomised control trials reported what?

Answer 75

reported a mean effect size of 0.16 across a range of interventions

Question 76

A recent review by Papp and colleagues (2009) including 10 randomised control trials reported a mean effect size of 0.16 across a range of interventions, although the authors noted what?

Answer 76

that most studies failed to include matched, active controls or placebos and that the benefit of the intervention often failed to generalize across varied cognitive outcomes.

Question 77

What is another problem with the literature on cognitive interventions?

Answer 77

few studies included a lengthy follow-up to determine whether any apparent short-term gains in cognitive test performance were reflected at a more distal time point.

Question 78

What will this area benefit from?

Answer 78

This area will benefit from increased scrutiny and well-designed trials.

Question 79

To conclude

Answer 79

there is certainly evidence that changes in behaviour can alter the trajectory of the decline of brain function.

Whether such changes can explain the dramatic individual differences found in the decline of brain function remains to be determined, but the evidence certainly points to them playing an important role; and as our population ages, such areas merit future research.