Cognition and Frailty in Older Adults: Evidence for a Possible Link: Frailty is a prevalent geriatric syndrome that results from a reduction in the reserves of multiple systems, leading to a state of increased vulnerability to stressors. Many epidemiological studies have reported that frailty increases the risk of future cognitive decline and that cognitive impairment increases the risk of frailty suggesting that cognition and frailty interact within a cycle of decline associated with ageing. The biological basis of frailty is complex. Frailty is a cumulative result of pathophysiological modifications caused by concurrent chronic conditions (e.g., cardiovascular and pulmonary disease, diabetes), subclinical adaptations of the systemic homeostatic mechanisms (e.g., inflammation, oxidative damage, and mitochondrial function), metabolic modifications, and behavioral factors (e.g., reduced physical activity). Interestingly, some of these pathways are shared by both frailty and Alzheimer's disease. The main risk factors that are generally implicated in both conditions are: high IL-6, obesity, hyperglycemia, low DHEA, anemia, and hypovitaminosis D. Therefore, treatment approaches that target the risk factors involved in the frailty cycle may be appropriate for prevention of incident cognitive impairment and vice versa

1. Cognition and Frailty inCognition and Frailty in
Older Adults: Evidence forOlder Adults: Evidence for
a Possible Linka Possible Link
Doha Rasheedy, MD
Lecturer of Geriatrics and Gerontology
Geriatrics and Gerontology Department
Ain Shams University

2. Frailty refers to a geriatric syndrome characterized
by loss of physiologic reserve, and increased
vulnerability to stressors leading to increased risk of
negative health-related events
The prevalence and the consequences of frailty
present a considerable burden to older people,
their carers, health care services and the
community.
(Houles M. et al.,2012)

3. However, data concerning the biological and
clinical basis of this syndrome are still limited.
To overcome the absence of clear biological and
clinical markers, researchers have been
developing various operational definitions aimed
at capturing the syndromic nature of this
condition.
(Houles M. et al.,2012)

4. Researchers focused on physical frailty in different
outcome models despite the multidimensional pattern of
the syndrome.
The relationship between frailty and cognition is of
growing importance. Cognitive impairment is increasingly
recognized as a potential contributor to the clinical
vulnerability of older persons, being a strong predictor of
several adverse health related outcomes.
(Sternberg SA; et al. 2011).

5. This Frailty definition is based on a scoring
system related to physical fitness not
including mood and cognitive status.
The Fried frailty modelThe Fried frailty model
Fried LP, Tangen CM, Walston J, et al. 2001Fried LP, Tangen CM, Walston J, et al. 2001

6. It includes disability, diseases, physical and
cognitive impairments, psychosocial risk
factors and geriatric syndromes (eg, falls,
delirium, and urinary incontinence)
The FI seems to be more sensitive in
predicting adverse health outcomes than the
Fried and colleagues’ physical phenotype.
Frailty indexFrailty index
Rockwood K et al., (2001)

8. The Edmonton frail scaleThe Edmonton frail scale
ROLFSON DB et al.,2006

9. COGNITIVE IMPAIRMENT AS ACOGNITIVE IMPAIRMENT AS A
COMPONENT OF FRAILTYCOMPONENT OF FRAILTY
Cognitive and physical function are closely
interrelated, and a measure of frailty that includes
cognitive performance, is a better predictor of
adverse-health outcomes
– Incorporating cognitive impairment improves the
predictive value of frailty for adverse outcomes

11. FRAILTY AS RISK FACTOR FORFRAILTY AS RISK FACTOR FOR
COGNITIVE IMPAIRMENTCOGNITIVE IMPAIRMENT
Cross-sectional studies have reported
associations between physical frailty and
cognitive function.
Higher level of physical frailty is associated with
an increased risk of incident MCI.
Frailty is predictive of incident AD and is
associated with the rate of cognitive decline

12. • Frailty was found to be a Prodromal Stage of
Vascular Dementia
Individual components of frailty; impaired grip
strength, slowed gait and low body mass index
(BMI), have been shown to predict development
of dementia and are associated with incident
MCI.
Stewart R et al.,2005
(Ávila-Funes et al., 2011)

14. Although physical frailty and cognitive
impairment have shown to be related in
epidemiological studies, their pathophysiological
mechanisms have generally been studied
separately.
Moreover, The mechanisms thatMoreover, The mechanisms that
underlie the relationshipsunderlie the relationships
between frailty and cognitivebetween frailty and cognitive
impairment remain unclearimpairment remain unclear.

15. The biological basis of frailty could be constituted as
the cumulative result of pathophysiological
modifications caused by:
1. Genetic variation
2. concurrent chronic conditions (e.g., cardiovascular and
pulmonary disease, diabetes),
3. subclinical adaptations of the systemic homeostatic
mechanisms (e.g., inflammation, oxidative damage),
4. metabolic modifications (hyperglycemia,
5. behavioral factors (e.g., reduced physical activity).
some of these pathways are shared by both frailty
and AD.
Walston J et al.,2006

16. Biologic model for frailty describing theBiologic model for frailty describing the
hypothesized molecular, physiological,hypothesized molecular, physiological,
and clinical pathways to frailtyand clinical pathways to frailty
)Walston, et al., 2006, pp.993(

17. Does cognitive frailty exist?
The similar model of physical frailty can be adapted
to the aged brain and the concept of cognitive frailty
applies to dysfunction of the neuron’s energetics and
the effects of this dysfunction on neuronal energy
production, survival and synaptic operations.
)Manton et al., 2004(

18. Does cognitive frailty exist?
CNS , muscle tissue are both high energy consuming tissues.
 CNS is very sensitive to circulatory dysfunction (caused by chronic
disorders), oxidative damage, and inflammatory cytokines which are
major predictors of physical frailty.
The mitotic index of neurons in adults is low making it difficult to
replace damaged neuronal cells than replacement of myocytes in
damaged muscle tissue.
)Manton et al., 2004(

19. Cognitive frailty is identified as a
heterogeneous clinical manifestation
characterized by the simultaneous
presence of both physical frailty and
cognitive impairment.

20. The key factors defining such a condition
include:
1) presence of physical frailty and cognitive
impairment (Clinical Dementia Rating score
of 0.5); and
2) exclusion of concurrent Alzheimer
disease dementia or other dementias.

21. The concept of “cognitive frailty” recognizes the
synergistic effect that Mild Cognitive Impairment
(MCI) have in persons with physical frailty on
adverse outcomes.
cognitive frailty may represent a precursor of
neurodegenerative processes. A potential for
reversibility may also characterize this entity. A
psychological component of the condition is
evident and participates at increasing the
vulnerability of the individual to stressors.

22. Addition of a cognitive assessment in the
operational definitions of frailty should be
carefully considered, being the cognitive
domain strongly associated with a wide
spectrum of adverse outcomes in the
elderly.
Future studies are needed to promote the
study of the proposed new syndrome of
cognitive frailty.

23. THANK YOUTHANK YOU