The Journal of Nutrition, Health & Aging©

Volume 17, Number 9, 2013

COMMENTARY

COGNITIVE FRAILTY: FRONTIERS AND CHALLENGES

A.J. WOODS, R.A. COHEN, M. PAHOR
Department of Aging and Geriatric Research, Institute on Aging, Cognitive Aging and Memory Clinical Translational Research Program, University of Florida, Gainesville, FL, USA.
Corresponding author: Adam J. Woods, PhD, Institute on Aging CTRB, Department of Aging and Geriatric Research, 2004 Mowry Road, University of Florida, Gainesville, FL 32611,
Phone: 352-294-5842, Email: ajwoods@ufl.edu

An international consensus group comprised of investigators The term has often been used as a general descriptor for
from the International Academy of Nutrition and Aging cognitive impairment occurring as people reach advanced age.
(IANA) and the International Association of Gerontology and Sometimes cognitive frailty refers to cognitive disturbances or
Geriatrics (IAGG) recently convened in Toulouse, France to pre-dementia occurring in association with other medical
establish a definition for cognitive frailty in older adults. This conditions (9). However, Kelaiditi et al. state that cognitive
effort was motivated by growing awareness that many people frailty must be considered as being independent of dementia or
with physical frailty are also prone to cognitive problems. In pre-existing brain disorders (1). Accordingly, there seems to be
“Cognitive Frailty: Rationale and Definition” (1), an initial several different perspectives on the nature of cognitive frailty.
working definition was developed, and a framework proposed The fact that the construct is ambiguous and lacking a precise
for future studies of cognitive frailty. operational definition clearly reinforces the authors’ effort to
This group should be commended for addressing the establish a common language for future studies of cognitive
construct of cognitive frailty and an obvious gap in the clinical frailty.
gerontology literature. Physical frailty is a widely recognized An obvious question emerges: How is cognitive frailty
problem in the elderly. While age-associated cognitive different from cognitive reserve? Cognitive reserve refers to the
dysfunction has been studied for many years, for the most part capacity of a given individual to resist cognitive impairment or
it was not conceptualized in a manner that is consistent with decline. Educational level and prior cognitive abilities have
current definitions of physical frailty. In fact, cognition has been shown to be important determinants of cognitive reserve
typically not been conceptualized in this manner, and only (10-12). Cognitive reserve has been linked with resilience of
recently has the term cognitive frailty been employed. brain function and structure in the presence of disease, injury,
Rockwood et al published one of the first studies to examine or other factors that alter physiological functioning (13). While
factors associated with frailty in the elderly (2). Frailty was cognitive and brain reserve undoubtedly have some common
conceptualized as a multidimensional construct with both underpinnings, the relationship between these types of reserve
physical and cognitive origins. Panza et al. used the term is still not fully understood.
cognitive frailty in the title of their review of pre-dementia Kelaiditi et al maintain that “cognitive frailty is
syndrome vascular risk factors (3). In a subsequent paper, characterized by reduced cognitive reserve”. Accordingly,
Panza et al, attempted to specify different models of frailty in cognitive frailty could be viewed as simply the inverse of
pre-dementia and dementia syndrome (4). The prognostic cognitive reserve. The authors indicate that while cognitive
accuracy of frailty assessment inventories for mortality among reserve is an important element of cognitive frailty, it is also
hospitalized elderly people was examined subsequently, with dependent on the existence of physical frailty; i.e., “the
results suggesting that both cognitive and physical factors were simultaneous presence of both physical frailty and cognitive
important in predicting outcome (5). We reviewed 199 impairment”. They distinguish this category of older non-
manuscripts cited in PubMed in which cognitive frailty was demented adults from cognitive impairment in the absence of
mentioned in either the title or as a keyword. In the vast physical frailty. The importance of this categorization is that it
majority of these manuscripts, frailty was examined as a emphasizes an important and often under-recognized
manifestation of cognitive dysfunction. Only recently has relationship between systemic physical illness, brain
cognitive frailty itself become the focus of inquiry. dysfunction, and cognitive impairment. It is now well
The term cognitive frailty is attractive as it suggests a established that cognitive disturbances occur secondary to
parallel with physical frailty. The concept of physical frailty is various medical conditions, such as cardiovascular disease,
relatively well understood in the context of aging, and has been diabetes and HIV (14-19).
operationalized in studies conducted over the past two decades The value of excluding brain disorders from cognitive frailty
(6-8). However, as Kelaiditi et al. point out, the operational may be less well justified. By limiting cognitive frailty to
definition of physical frailty remains unresolved (1). The people with physical frailty, Kelaiditi et al create four discrete
situation is even more problematic for cognitive frailty, as past categories of older non-demented adults, which may have some
investigators have focused on a variety of different phenomena. clinical value. However, with respect to the concept of
Received July 20, 2013
Accepted for publication July 30, 2013
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Volume 17, Number 9, 2013

COGNITIVE FRAILTY: FRONTIERS AND CHALLENGES

cognitive frailty, there are many examples of people who are In sum, “Cognitive Frailty: Rationale and Definition” (1)
vulnerable to subsequent functional decline based on the provides a valuable starting point for the development of a
existence of subtle cognitive and/or brain abnormalities below coherent operational definition and for future studies of
the threshold for clinical detection. In fact, a major thrust of cognitive frailty. While closely linked to cognitive reserve, the
current research on neurodegenerative disease focuses on the construct of cognitive frailty goes beyond cognitive reserve,
discovery of vulnerability and early markers of future particularly because of its association with physical frailty and
functional decline. While physical disorders such as diabetes the fact that it often becomes evident in the context of acute
and cardiovascular risk factors contribute to this vulnerability, a physical illness. There seems to be considerable value in
variety of neurobiological and behavioral risk factors also exist distinguishing vulnerability to cognitive functional decline
that create functional vulnerability (20-22), and ultimately among people with or without physical frailty, though there is
cognitive frailty. In fact, excluding people with brain evidence that both cognitive and physical frailty share several
disturbances from the definition of cognitive frailty fails to common pathophysiologic mechanisms and risk factors.
account for the fact that the effects of physical illnesses are Growing and consistent epidemiologic evidence shows that
exacerbated by the existence of a neural predisposition to impaired physical performance, which is a component of
cognitive decline or prior brain disturbances that reduce physical frailty, measured with walking speed or the Short
cognitive reserve. Furthermore, people with physical frailty Physical Performance Battery (SPPB) (23), is independently
who develop cognitive frailty presumably do so as their brain associated with cognitive decline (24-36). The SPPB tests,
begins to develop neuropathological changes. Accordingly, including walking, balance and chair stands, require the
there is value in dichotomizing cognitive frailty between people complex interplay of sensory, cognitive, and motor functions.
with or without pre-existing brain dysfunction, or alternatively These systems may be altered early in the path to cognitive
treating brain vulnerability as a mediator of the effects of decline (36, 37), and possibly to cognitive frailty. Low walking
physical illness on cognitive frailty. speed and low SPPB score are also associated with elevated
Defining cognitive frailty depends on determining its inflammatory cytokines and low Brain-Derived Natirurectic
diagnostic criteria. Other than physical frailty, the primary Factor (BDNF) (38-40), all of which are predictors of cognitive
criteria proposed by Kelaiditi et al. is the presence of mild decline (41, 42).
cognitive impairment as defined by a clinical dementia rating Future research is needed to determine how phenotypic
(CDR) score of 0.5, without Alzheimer’s disease or another differences among people and the existence of a wide variety of
progressive brain disturbance that would lead to dementia. preexisting manifestations of brain structure and function affect
Using these criteria, it is not clear whether people with this vulnerability. Following the expert consensus, prospective
cerebrovascular disturbances would meet these criteria or not. studies will be needed to assess the reliability and predictive
The authors make a point of also noting that “under different validity of the operational measure of cognitive frailty. We laud
circumstances cognitive frailty may also represent a precursor the efforts of the IANA/IAGG consensus group in laying the
of neurodegenerative processes”. This is a critical point that foundation for the emerging concept of cognitive frailty and
reinforces the need to go beyond the definition of cognitive strongly encourage future studies aimed at advancing this
frailty as occurring in the absence of brain dysfunction. It is clinical domain.
also likely that a CDR = 0.5 is too narrow to fully capture the
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JNHA: COGNITIVE FRAILTY

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