Cognitive development and aging

1. COGNITIVE DEVELOPMENT AND
AGEING

2. LIFE EXPECTANCY
• Increased population life
expectancy
• Increase in disease
prevalence
• Increase in care consumption
• Loss of independence and
quality-of-life

3. COGNITION
 Cognition is the set of all mental abilities and processes related to
knowledge: attention, memory and working memory, judgment and
evaluation, reasoning, problem solving, decision making, comprehension and
production of language.
 These processes are not independent of one another – E.g. attention may be
part of perception; language may be part of memory and decision-making, etc.

4. NEUROCOGNITIVE DOMAINS
The DSM-5 defines six key domains of cognitive function, and each of these has
subdomains.

5. Cognitive development

6. BRAIN DEVELOPMENT
Timeline of major events in brain
development. This diagram
represents brain development
beginning with neurolation, and
proceeding with neuronal
migration, synaptogenesis,
pruning, myelination, andcortical
thinning. Reproduced with
permission and modified from
Giedd(1999) (Copyright 1999)
American Psychiatric Association.

8. GMD: Gray matter density
GMV: Gray matter volume
GMM: Gray matter mass
CT: Cortical thickness

9. LONGITUDINAL DEVELOPMENT OF HUMAN BRAIN WIRING CONTINUES FROM
CHILDHOOD INTO ADULTHOOD: CATHERINE LEBEL AND CHRISTIAN BEAULIEU. JOURNAL
OF NEUROSCIENCE 27 JULY 2011, 31 (30) 10937-10947 Changes of white matter, gray
matter, and total brain volume
with age for each scan are shown
(top row) along with bar graphs
reflecting the percentage of
subjects with volume increases
(green), decreases (red), or no
change (blue) within six age
categories.
• White matter volume
increased significantly across
the age range, including the
twenties,
• Gray matter volume
decreased in the majority of
children, adolescents, and
young adults up to 25 years.
• These white matter increases
and gray matter decreases
offset one another such that
total brain volume did not
change in most persons,
although many of the younger

11. BRAIN DEVELOPMENT
 brain development can be divided into three processes:
• Proliferation:
(rapid growth of brain matter and the formation of new connections within the brain).
• Pruning:
(cutting away of unused or unimportant connections).
• Myelination:
(insulating of brain pathways to make them faster and more stable) )
(Sowell et al., 1999; Sowell et al., 2001)

12. PROLIFERATION: TOTAL BRAIN VOLUME
 By age 6, the brain is about 95%
of its maximum size.
 It reaches its maximum size at
11.5 years in girls, and at 14.5
years in boys. (Giedd et al., 1999)
 Boys brains are larger (on
average) than girls brains

13.  Maximum brain size does not mean maximum brain
maturity!
 The brain continues to mature for at least another 10 years.
 And although boys brains are anatomically bigger than girls
brains, size is not directly related to intelligence.
 Grey matter is where all the thinking happens. This is your
brain’s processing center.
 White matter, containing those long axons, are like a super
highway. They transport information to different parts of
your brain.

14. PRUNING: GREY MATTER MATURATION
 The brain matures in a back-to-front
pattern. The frontal & temporal lobes
are the last to mature.
 Remember: the frontal lobe is the
home of planning, organization,
judgment, impulse control and
reasoning.
 The developmental trajectory of
cortical gray matter followed a
regionally specific pattern with areas
subserving primary functions, such as
motor and sensory systems, maturing
earliest and higher order association
areas, which integrate those primary
functions, maturing later.
For example, in
the temporal lobes the latest part to
reach adult levels is the
superior temporal gyrus/sulcus which
integrates memory,
audio-visual input, and object
recognition functions

15. PROLIFERATION AND MYELINATION: WHITE MATTER
Mie Matsui et al. Age-related Volumetric Changes of
Prefrontal Gray and White Matter from Healthy
Infancy to Adulthood. International Journal of
Clinical and Experimental Neurology, 2016, Vol. 4,
No. 1, 1-8.
Plot of the predicted volume of total GM, total WM, and total CSF by
age
• White matter makes up myelin,
which insulates axons and speeds up
the communication between
neurons.
• It develops continuously from birth
onwards, with a slight increase
during puberty.
• The increase occurs just after the
peak in grey matter volume (around
age 11 in girls* and around age 13 in
boys).

16. AGAIN !!!!

17. COGNITIVE DEVELOPMENT
Hudspeth, W. J., and Pribram, K. H. (1990). Stages of brain
and cognitive maturation. J. Educ. Psychol. 82, 881–884.
Crystallized and fluid intelligences evolve differently across
the lifespan.
Li, S.-C., Lindenberger, U., Hommel, B., Aschersleben, G., Prinz, W., and Baltes, P.
B. 2004. Transformations in the couplings among intellectual abilities and
constituent cognitive processes across the life span. Psychol. Sci. 15:155–63

18. COGNITIVE FUNCTIONS AND AGING
Cross-sectional aging data
adapted from Park et al.
(2002) showing behavioral
performance on measures of
speed of processing,
working memory, long-term
memory, and world
knowledge. Almost all
measures of cognitive
function show decline with
age, except world
knowledge, which may even
show some improvement.
Park DC, Lautenschlager G, Hedden T, Davidson NS,
Smith AD, Smith PK. Models of visuospatial and
verbal memory across the adult life span. Psychol
Aging. 2002;17(2):299–320.

20.  On an average aging is accompanied by decline in three fundamental cognitive-
processing resources:
1. Processing Speed: reduced speed of information processing and response- most predictable
2. Working Memory: refers to short-term retention and manipulation of information held in
conscious memory, a type of “online” cognitive processing. exa. Examples include consciously
recalling a telephone number long enough to write it down
3. Sensory and Perceptual changes: decrements in visual and auditory acuity and other
perceptual changes.

21. NEUROPLASTICITY
(YOU CANN’T TEACH AN OLD DOG A NEW TRICK)
 Neuroplasticity: The brain's ability to reorganize itself by forming new neural connections throughout life.
Neuroplasticity allows the neurons (nerve cells) in the brain to compensate for injury and disease and to
adjust their activities in response to new situations or to changes in their environment.
 Exists at all levels of the brain (in cells, genes, behavior)
 Neuroplasticity occurs through three main mechanisms – myelination, synaptic connection and
neurogenesis.
 Every time we change our habits, learn something new, change our mind about how we think of the world,
stop an addiction, and so on, we have literally dismantled an old neural network, and created a new one
that has a new way of thinking wired into it, one that rewards us in a healthier way. Learning new skills –
such as a new language, or a physical skill like riding a bicycle, playing music and such, creates new brain
wiring as wel

23. NEUROPLASTICITY AND AGE

24. THEORIES OF AGING
1- THE PROGRAMMED THEORY :
has three sub-categories:
1) Programmed Longevity. Aging is the result of a sequential switching on and off of certain
genes, with senescence being defined as the time when age-associated deficits are manifested.
2) Endocrine Theory. Biological clocks act through hormones to control the pace of aging.
Recent studies confirm that aging is hormonally regulated and that the evolutionarily conserved
insulin/IGF-1 signaling (IIS) pathway plays a key role in the hormonal regulation of aging.
3) Immunological Theory. The immune system is programmed to decline over time, which leads
to an increased vulnerability to infectious disease and thus aging and death.
Theories of Aging. (2016, February 13). Physiopedia, Retrieved 09:41, May 2, 2018 from https://www.physio-pedia.com/index.php?
Title = Theories_of_Aging&oldid=133555.

25. 2- THE DAMAGE OR ERROR THEORY
include:
1) Wear and tear theory. Cells and tissues have vital parts that wear out resulting in aging. Like
components of an aging car, parts of the body eventually wear out from repeated use, killing them and
then the body.
2) Rate of living theory. The greater an organism’s rate of oxygen basal metabolism, the shorter its life
span.
3) Cross-linking theory. The cross-linking theory of aging was proposed by Johan Bjorksten in 1942.
According to this theory, an accumulation of cross-linked proteins damages cells and tissues, slowing
down bodily processes resulting in aging.
4) Free radicals theory. proposes that superoxide and other free radicals cause damage to the
macromolecular components of the cell, giving rise to accumulated damage causing cells, and eventually
organs, to stop functioning.
Theories of Aging. (2016, February 13). Physiopedia, Retrieved 09:41, May 2, 2018 from https://www.physio-pedia.com/index.php? Title =

26. 5) Somatic DNA damage theory. DNA damages occur continuously in cells of living organisms.
While most of these damages are repaired, some accumulate, as the DNA Polymerases and other
repair mechanisms cannot correct defects as fast as they are apparently produced.
6) Telomere Shortening. Telomeres are
repeated nucleotides sequences on the end
of chromosomes that are believed to protect
the DNA strands and prevent them from
fusing with other strands. Telomeres lose a
little bit of their length during each cell
division. Since replicative DNA polymerases
are not able to replicate telomeres, telomeres
become too short to replicate after a fixed
number of cell divisions. Eventually, the cell
will stop growing and enter cellular

27. MITOCHONDRIAL DYSFUNCTION
The most common form of cell death in neurodegeneration is through the intrinsic
mitochondrial apoptotic pathway.
mild mitochondrial
dysfunction:
 stimulates retrograde
signaling,
 increasing the
production of
antioxidant enzymes
and
 inducing metabolic
changes. This adaptive
response leads to the
extension of the
lifespan of the
On the contrary,
severe disturbance of
the mitochondrial
activity:
 compromises
energy production,
 induces oxidative
stress and
 disturbs calcium
homeostasis.
 rapid changes of
the dendritic
structures and, Cell
death programs.

28. COGNITIVE RESERVE
 The term cognitive reserve describes the mind's resistance to damage of the brain.
 Various studies have shown that there is major variation in the clinical manifestations and
severity of cognitive aging as a result of neurodegenerative changes that are similar in nature
and extent. These mismatches led to the emergence of the concept of cognitive reserve (CR),
which focuses on the adaptability and the flexible strategies of the brain that allow some
people to cope better than others in the circumstance of age-related or Alzheimer's disease
(AD)-related pathology. It is believed that CR is mainly influenced by an individual's education,
intellect, mental stimulation, participation in leisure activities, dietary preferences, and social
stimulation. These determinants of CR help in slowing the rate of memory decline in the
normal aging process and also reduce the risk of developing AD.

29. BRAIN RESERVE - "THE HARDWARE“
THE QUANTITATIVE MODEL
 Brain reserve (BR) is an element of the "threshold model" or the passive model.
 According to this model, there is a fixed threshold value at which functional impairment
manifests for everyone.
 The brain's size, the neuronal count, and the synaptic density form the basis of BR.
 Larger brains, due to sufficient neural substrate, are able to sustain more insult till symptoms
emerge. A brain insult of a particular size might cause a clinical deficit in an individual with
less BRC, whereas it may not cause any deficit in individuals with greater BRC.

30. COGNITIVE RESERVE - "THE SOFTWARE“
THE QUALITATIVE MODEL
 Cognitive reserve (CR), on the other hand, constitutes the active model
 According to this model the brain copes with damage by using either preexisting cognitive
processes to increase the efficiency and capacity of existing neural pathways or by using
compensatory processes to recruit new pathways that are usually not used while
accomplishing a task.
 Thus, a person with a greater CR may be able to sustain a larger lesion than a person with
lesser CR before clinical symptoms start appearing, even though both may have the same
BRC.

31. Illustration of the association
between the emergence of
dementia-associated
neuropathology, its clinical
expression and cognitive reserve.
Educational attainment and
occupational challenges can
usually no longer be changed in
individuals aged 50 years and
older. However, cognitive leisure
activities may increase their
cognitive reserve and thus lead
to a delay in the emergence of
cognitive decline.
Sattler C, Toro P, Schönknecht P, Schröder J.
Cognitive activity, education and
socioeconomic status as preventive factors for
mild cognitive impairment and Alzheimer’s
disease. Psychiatry Res. 2012;196(1):90–5.

32. WHEN AD PATHOLOGY IS MILD, INDIVIDUALS WITH LOWER LEVELS OF RESERVE MIGHT ALREADY APPEAR TO BE
CLINICALLY DEMENTED, WHILE THOSE WITH HIGHER RESERVE MIGHT APPEAR CLINICALLY NORMAL. AT HIGHER
LEVELS OF PATHOLOGY, BOTH GROUPS MIGHT APPEAR TO BE CLINICALLY DEMENTED.
Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer’s disease.
Lancet Neurology, 11(11), 1006–1012. http://doi.org/10.1016/S1474-
4422(12)70191-6

33.  The broken green line (1) represents
the “normal” situation.
 There is loss of cognitive function
with aging until a threshold point is
crossed (broken red line) resulting
clinically in dementia.
 After an episode of traumatic brain
injury there is a significant decline in
cognitive function which recovers, the
degree of recovery being dependent
on the severity of the head injury.
 Recovery is, however, not complete
resulting in a loss of functional
reserve. After this point cognitive
decline may be as for normal ageing
[broken blue line (2)] with the
dementia threshold being crossed
earlier due to loss of functional
reserve, or there may be a continued
synergistic effect of mechanisms
initiated by the head injury which
accelerates cognitive decline [broken
Smith, C. (2013). Review: the long-term consequences of microglial activation
following acute traumatic brain injury. Neuropathol. Appl. Neurobiol. 39, 35–44.

34. DETERMINANTS OF COGNITIVE RESERVE
 Cognitive engagement and stimulating activities
 In a study of 65 healthy older individuals, it was found that individuals with greater
early and middle life cognitive activity (reading, writing, playing games, physical
exercise) had lower Pittsburgh Compound B (PiB) on positron emission tomography
(PET) scan studies. [8] The study found that lifestyle factors found in individuals with
high cognitive engagement may prevent or slow the deposition of β-amyloid,
resulting in slower progress to AD.
 Another measuring factor of cognitive engagement could be bilingualism. bilinguals
required greater amounts of neuropathology before the disease manifested.
 instrumental musical experience across the life-span. Cognitive functioning in old age
was found to have a linear relation to the number of years of musical participation.
 social isolation as a risk for cognitive decline. The risk of AD was found to be more
than double in lonely persons as compared with those who were not.

35. Scaled scores for significant between-group results. VR II = Visual Reproduction Delayed Recall; BNT = Boston
Naming Test.
Hanna-Pladdy, B., & MacKay, A. (2011). The Relation Between Instrumental Musical Activity and Cognitive Aging. Neuropsychology, 25(3), 378–386.
http://doi.org/10.1037/a0021895

36. COGNITIVE REMEDIATION
 Cognitive remediation.
 It is a behavioral treatment that aims to enhance the compensatory and adaptive strategies
to facilitate improvement in specific brain areas such as attention, memory, judgment, speed
of information processing, and problem solving.
 The training activities consist of computerized exercises and real-time strategy-based video
gaming. This treatment is reported to enhance executive functioning in the elderly.
 Education
Education may indirectly help in increasing the CR by reducing the impact of
neuropathological lesions during aging. Even a few years of formal education is associated
with decreased impairment in cognitive functioning as compared to no formal education at
all, irrespective of the socioeconomic and demographic characteristics of a population.

37. DRS scores of CVS
patients at admission to
rehabilitation and at 1
year Mean (95%
confidence interval)
Disability Rating Scale
(DRS) scores on
admission to
rehabilitation and at 1
year in patients grouped
by years of education.
Schneider, E. B., Sur, S., Raymont, V., Duckworth,
J., Kowalski, R. G., Efron, D. T., … Stevens, R. D.
(2014). Functional recovery after moderate/severe
traumatic brain injury: A role for cognitive
reserve? Neurology,

38.  Role of leisure activities
Various epidemiological studies have demonstrated that late-life mental
stimulation activities are reported to aid in better cognitive functioning.
 Social network and stimulation
Social support and networking provide psychological and material resources
that are usually intended to benefit an individual's ability to cope with stress.
A number of social parameters such as marital status, number of children,
frequency of meeting family members and relatives, living arrangements,
satisfaction with life have been studied. Other variables such as attending
social functions, participating in religious activities, and having a part-time or
full-time job are equally important.

39. The change in cognitive function across disease pathologies was more pronounced for people with smaller
social network sizes than for those with larger ones.

41. HEALTH AND COGNITION
 Brain depends on multiple organ systems for O2, glucose and nutrient supply
 Sensitive to metabolic disturbances
 Many diseases & pharmacological therapies have impact on brain function
 Heath insults on cognitive function
 Hypertension [Starr, 1992; Waldstein, 1995]
 Cardiovascular diseases [Elias, 1990; Skoog, 1994]
 Obstructive pulmonary disease [Incalzi, 1993]
 Diabetes [U'ren, 1990; Widom, 1990]
 Renal failure [Moe, 1994]
 Liver failure [Tarter, 1988]
 Cancer [Berg, 1988]
 Thyroid hypo-/hyperfunction [Beckwith, 1988]
 Endocrine disorders (e.g. Cushing’s syndrome)

42. Major mechanisms underlying vascular cognitive impairment (VCI). A, Vascular causes. B, Brain
parenchymal lesions associated with VCI. WML indicates white matter lesion (graphical realization: Antonia
Weingart, Institute for Stroke and Dementia Research).

43. (MR) imaging changes associated
with vascular cognitive
impairment (VCI).
• A, (FLAIR) image of a patient
with vascular dementia (VaD)
showing extensive white matter
hyperintensities (white arrows)
and a lacune in the right frontal
white matter (white
arrowhead).
• B, T2*-scan of a patient with
VCI, demonstrating 2
microbleeds in the left occipital
cortex (black arrowhead) as
well as superficial siderosis in
the frontal cortex
predominantly on the right
side (black arrowhead); inset:
FLAIR image of the left frontal
cortex displaying an enlarged
perivascular space. In both
cases, there is some indication
of brain atrophy as reflected by

44. Schematic interplay of pathogenic factors causing vascular cognitive impairment/dementia.

45. Strength of evidence on risk factors for cognitive decline

46. The Global Composite cognitive score increased significantly as health levels
increased from poor to ideal, for smoking, BMI, and physical activity (p for linear
trend <0.05, for all).
Cardiovascular Health and Cognitive Function: The Maine-Syracuse Longitudinal Study Georgina E. Crichton, Merrill F.
Elias, Adam Davey, Ala'a Alkerwi

47. The number of Alzheimer's disease (AD) cases that could potentially be prevented through risk
factor reductions of 10% or 25% worldwide
Barnes, D. E., & Yaffe, K. (2011). The Projected Impact of Risk Factor Reduction on Alzheimer’s Disease Prevalence. Lancet Neurology, 10(9), 819–

48. The likely developmental trends across the human lifespan (an inverted U-shape). The down-turning paths are for normal aging,
cognitive aging, and successful aging in motor and cognitive functions. Overall, the functional curves are moving downwards
during older adulthood. The slope of functional change is subject to a number of biological and environmental factors.

49. SUCCESSFUL COGNITIVE AGING
 Definition:
 ‘‘Not just the absence of cognitive impairment, but the development and preservation of the multi-
dimensional cognitive structure that allows the older adult to maintain social connectedness, and
ongoing sense of purpose, and the abilities to function independently, to permit functional recovery
from illness and injury, and to cope with residual cognitive deficits.’’
2006 National Institutes of Health’s Cognitive and Emotional Health Project (Hendrie et al.
2006).

50. DETERMINANTS OF SUCCESSFUL COGNITIVE AGING
 Genetic Influences
a number of studies have assessed the degree to which genes influence aging-related trajectories in cognitive
health. Among twin studies, there does appear to be evidence that cognitive performance in later life is
heritable.
(a) genes involved in cardiovascular health and cholesterol, lipid, and lipoprotein transport or metabolization
(e.g., PON1, APOE), (b) genes involved in inflammatory processes (e.g., IL6, IL10), and (c) genes involved in
cell cycling, growth, and signaling (e.g., SIRT3).
 Stress and Resilience
It is clear that chronic unremitting stress in older adults influences a network of physiological processes that
often results in neuronal degradation. Specifically, the stress-associated stimulation of the Hypothalamic-
Pituitary-Adrenal axis results in the secretion of glucocorticoids such as cortisol, which is associated with
damage to various brain structures, and particularly the hippocampus.

51.  Brain Reserve and Cognitive Reserve
 Lifestyle Behaviors
 Physical Activity
 Nutrition/Dietary Restriction
 Cognitive Stimulation
 General Health improvement (BP, Diabetes, Smoking, Hyperlipidemia, etc…)

52. TAKE HOME MESSAGES
 Aging doesn’t mean dementia
 Old brains are quite vulnerable, but:……..
 Your brain is a mirror of your health
 The more mentally active, the less cognitively vulnerable you are
 Let your social network go bigger and bigger