Cognitive frailty: Operationalisation of the concept and the study of comorbidities as possible risk factors

Onderzoeksoutput: PhD Thesis

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In the context of population ageing, age prevalent conditions such as major neurocognitive disorders are becoming a public health concern. To add injury to insult, treatments which cure, or reverse dementia are as yet unavailable. Therefore, knowledge and insights about relatively new health conditions such as cognitive frailty (CF) which predispose older adults to the risk of adverse health outcomes including incident dementia are urgently needed. A typical feature of CF is that it is potentially reversible and thereby an ideal target for prevention intervention strategies to reduce the gap between life span and healthy years. Despite the usefulness of CF in minimising the burdensome consequences of dementia by decelerating the frailty-disabling cascade, there are two main niches concerning CF that, as yet, have not been amply explored. The first gap in ageing research concerns the standardisation of CF operationalisation and the second concerns modifiable risk factors (RFs) associated with cognitive impairment (CI) and CF in the oldest old. Therefore, the first part of this doctoral thesis focused on the concept and operationalisation of frailty and its subtype CF. It aimed to expose the heterogeneity of frailty operationalisation in older adults by comparing the frailty assessment tools to a globally recognised standardised framework of function called the International Classification of Functioning, Disability and Health (ICF). Since the principal focus of this doctoral research was CF, our research zoomed in on cognitive assessment methods applied in the identified frailty instruments. The second part of this thesis focused on RFs associated with cognitive decline/CF. Therefore, the relationship between prevailing modifiable RFs such as age-related hearing loss (ARHL) and vascular variables (RFs and morbidity) and cognitive decline/CF was explored.

In the first systematic review (CHAPTER 2), 79 frailty instruments were identified and subcategorised as single (32%) and multi-domain (68%). In the single-domain subgroup, 60% of the frailty instruments were based on the original or adapted version of the Frailty Phenotype model as proposed by Fried and colleagues (FFP). On the other hand, in the multi-domain group, 60 % were health deficit accumulation frailty instruments while the rest were health deficit indexes. For the first time in this doctoral thesis, the ICF was used as a reference framework to provide novel insight concerning which areas of the bio-psycho-social model of frailty are commonly shared among the frailty instruments and which are under-represented or completely absent. Body Functions (chapter 1: mental functions and chapter 5: functions of the digestive, metabolic and endocrine systems) and
208Activities and Participation (chapter 4: mobility and chapter 5: self-care) which form part of one’s intrinsic capacity were most frequently linked to frailty items. Extrinsic characteristics that complement one’s intrinsic capacity to determine function or lack thereof, represented by the Environmental component, barely featured in the mapping process. Co-morbidity which in principle belong to a separate entity than frailty featured frequently among the frailty instruments. Only the minority of frailty items could not be mapped to a suitable ICF code.

Our results corroborated what is already known in literature – mainly that there are two main approaches to evaluate frailty known as the FFP (a biological syndrome) and Frailty Index (FI) (multidimensional risk state) but also exposed the several adaptations available. Our detailed and comprehensive itinerary of frailty instruments may be used as a reference handbook by clinicians when considering the most suitable frailty instrument in their clinical endeavours in order to improve patient-centred care and better allocation of treatment intensity among patients of different frailty status. Moreover, this review showed that in many frailty instruments, deficits in basic self-care were applied in the context of identifying frail individuals and not as a measure of adverse frailty outcomes. This inconsistency whereby certain frailty instruments consider deficits in basic self-care as a risk factor and others as an adverse outcome of frailty complicates the issue of frailty evaluation and contributes to frailty operationalisation heterogeneity. Our review provided novel insights to researchers and clinicians as to which frailty instruments consider frailty and disability to be same entities and thereby to choose other frailty evaluation tools if possible. This review revealed that frailty subdomains such as social frailty and CF are currently under-represented. Focusing on CF which is the main topic of this thesis, this review showed that while mental functions and mental health conditions such as dementia feature quite regularly in frailty instruments, subtle cognitive deficits characteristic of the mild cognitive impairment (MCI) component of CF do not. Inclusion of advanced activities of daily living (a-ADL) such as hobbies and working in frailty evaluation instruments, represented across all the chapters of the ICF component Activities and Participation except for chapter 7 would be a step in the right direction to cover the MCI component of CF.
Since the ICF considers function as resulting from an interaction between one’s intrinsic capacity and their external environment it is very apt to be used as a reference framework
Activities and Participation(chapter 4: mobility and chapter 5: self-care) which form part of one’s intrinsic capacity were most frequently linked to frailty items. Extrinsic characteristics that complement one’s intrinsic capacity to determine function or lack thereof, represented by the Environmental component, barely featured in the mapping process. Co-morbidity which in principle belong to a separate entity than frailty featured frequently among the frailty instruments. Only the minority of frailty items could not be mapped to a suitable ICF code. Our results corroborated what is already known in literature –mainly that there are two main approaches to evaluate frailty known as the FFP (a biological syndrome) and Frailty Index (FI) (multidimensional risk state) but also exposed the several adaptations available. Our detailed and comprehensive itinerary of frailty instruments may be used as a reference handbook by clinicians when considering the most suitable frailty instrument in their clinical endeavours in order to improve patient-centred care and better allocation of treatment intensity among patients of different frailty status. Moreover, this review showed that in many frailty instruments, deficits in basic self-care were applied in the context of identifying frail individuals and not as a measure of adverse frailty outcomes. This inconsistency whereby certain frailty instruments consider deficits in basic self-care as a risk factor and others as an adverse outcome of frailty complicates the issue of frailty evaluation and contributes to frailty operationalisation heterogeneity. Our review provided novel insights to researchers and clinicians as to which frailty instruments consider frailty and disability to be same entities and thereby to choose other frailty evaluation tools if possible. This review revealed that frailty subdomains such as social frailty and CF are currently under-represented. Focusing on CF which is the main topic of this thesis, this review showed that while mental functions and mental health conditions such as dementia feature quite regularly in frailty instruments, subtle cognitive deficits characteristic of the mild cognitive impairment (MCI) component of CF do not. Inclusion of advanced activities of daily living (a-ADL) such as hobbies and working in frailty evaluation instruments, represented across all the chapters of the ICF component Activities and Participation except for chapter 7 would be a step in the right direction to cover the MCI component of CF. Since the ICF considers function as resulting from an interaction between one’s intrinsic capacity and their external environment it is very apt to be used as a reference framework 209for critically analysing the available frailty instruments in terms of the subdomains that they cover. Moreover, the ICF may be used to develop core sets relating to cognitive aspect of CF (a-ADL). However, at this preliminary stage, we conclude that the ICF is too extensive and laborious to replace the current frailty instruments in clinical practice. Considering that CF is a relatively new topic which is gaining attention and that the results attained from our first review exposed the frequent manner in which mental functions feature in frailty instruments, in CHAPTER 3different cognitive evaluation methods applied in the instruments which measure frailty were evaluated and compared to the original concept of CF as proposed by the International Academy of Nutrition and Aging (I.A.N.A) and the Association of Geriatrics and Gerontology (I.A.G.G) consensus group. The search identified 79 articles describing 92 frailty instruments. In total, less than half (46%) of the identified frailty instruments included assessment of the cognitive domain. The latter were categorised into 7 subgroups: dementia as co-morbidity (20%), objective cognitive screening tests such as MMSE (19%), signs and symptoms of CI such as memory loss interfering with activities (14%), delirium or clouding of consciousness (10%), self-reported such as ‘do you have problems with memory?’ (9%), non-specific cognitive dysfunction terms such as history relevant to CI or loss (8%), and a combination of the above (20%). Even though the definition of CF specifically excludes the presence of established dementia, this was the most common method of cognitive assessment in the available frailty instruments. Moreover, objective neuropsychological tests employed in the available frailty instruments mostly measured global cognition, memory and orientation whereby a study analysing the neuropsychological profile of CF subjects showed that the cognitive domains affected relate to executive and attention tasks reflecting a subcortico-frontal profile of cognitive decline which is different to that in Alzheimer dementia (AD). Although there is accordance on the fact that the co-occurrence of MCI and physical frailty (CF) increases the risk of incident dementia compared to physical frailty or CI alone, at the moment there is paucity in literature concerning whether the MCI component of the novel CF (that is, CI secondary to physical causes) and the well-researched amnestic MCI which is the precursor of AD refer to the same or different concept and therefore whether they necessitate different neuropsychological test batteries to be diagnosed.
The innovative information revealed by this review shows that although it is encouraging to see that CI assessment is being more frequently included in frailty operationalisation, tangible and robust information on the neuropsychological profile characterising CF and which dementia subtypes may result as CF progresses is urgently needed in order to encourage researchers and clinicians to adopt and spread the concept of CF – an essential first step in the process of promoting healthy ageing. Although standardisation of CF evaluation methods is a fundamental step for CF to be used as a target for prevention intervention strategies in the quest for healthy ageing promotion, an equally important action is to decelerate progression from CF to dementia by targeting RFs associated with CF. Considering the major relevance of hearing loss in the context of dementia prevention, in this doctoral thesis its relevance as a risk factor for CF - a potential prodromal stage of dementia – was explored in the oldest old. Since several vascular risk factors have been implicated as RFs for dementia, in this doctoral thesis their relevance in the context of the oldest old with CF was explored. Knowledge concerning RFs associated with CF is still in its infancy.
Thereby in CHAPTER 5 we studied the correlational strengths between hearing impairment (HI) and cognitive function as a proxy for hearing aid (HA) effects was studied in a sample of 126 physically non-frail community dwelling octogenarians. Exclusively within the non-HA users’ group (n=100), an association was found between HI and decline in global and domain-specific cognitive functions including processing speed and selective and alternating attention even after correcting for certain potential confounders - age and peripheral hearing loss severity. When further subdivided according to sex, the previous finding was only observed in male non-HA users. Furthermore, when the association between hearing loss and cognitive function was compared between the HA-users and non-HA users, we noted intergroup differences in the correlations between global cognition (MMSE) and peripheral (Pure-tone average PTA) and central (speech recognition threshold SRT) hearing impairment. This may be explained by the cascade hypothesis: in the presence of HI and effortful listening, recruitment of cognitive reserves to process degraded auditory stimuli exert strain on complementary cognitive domains including executive function and working memory. In the acute phase, cognitive recruitment results in temporary cognitive decline which is potentially reversible. However, in the presence of lengthier hearing loss trajectory, chronic neuroplastic changes occur in various cortical regions to accommodate for the persistent degraded auditory input leading to chronic loss of cognitive function. In males, the higher prevalence and longer trajectories of hearing impairment further exacerbate this cascade. Therefore, HA use may possibly interrupt this vicious circle and thereby curtail the trajectory of cognitive decline among those with HI. This study provides novel information concerning the influence of HA use on the relationship between HI and cognitive decline among the oldest old. This study provided innovative insights into possible ways to prevent or at least delay cognitive decline as up till to date this knowledge did not cover the oldest old population subgroup. In clinical practice, knowledge derived from our study may be utilised to increase awareness among healthcare professionals as well as the older adults themselves that the benefits of timely identification and correction of hearing loss extend beyond improvements in communication and social life to include cognitive health. Additionally, knowledge from our study may be used by healthcare professionals while fitting HAs to educate and encourage especially older men who tend to be less complaint to the regular use of HAs as uncorrected hearing loss may have detrimental consequences on their mental health and eventually on their functional independence. Since certain vascular risk factors such as hypertension, alcohol misuse and obesity in midlife and diabetes and smoking in late life have been identified as modifiable RFs for dementia, in CHAPTER 6 the association between vascular variables (RFs and morbidity) and potentially reversible CF in octogenarians was studied. Among our well-functioning study participants, the prevalence of CF was documented to be 27.3%. The presence of the metabolic syndrome (MetS) and altered mood states – two easily identifiable and modifiable RFs with great potential to be used as targets for prevention intervention strategies in the quest for promoting healthy ageing – were associated with CF. Our novel results highlight the importance of shifting the focus from classic single cardiovascular RFs or clinical cardiovascular disease to composite cardiovascular RF variables in particular MetS as this has been shown to be associated with CF and thereby potentially carries a higher risk for dementia. Since CF is very common (approximating 1 in 4) even in our exclusive cohort of well-functioning oldest old, we hypothesize that it is even more prevalent in a more representative cohort of  80 years older adults. The preliminary innovative results associating the metabolic syndrome with CF may serve to alert clinicians caring for older adults to the possible benefits derived from identifying and managing the metabolic syndrome that extend beyond the notion of decreasing cardiovascular related mortality to include preservation of cognitive health.
212This doctoral thesis in part focused on the operationalisation of frailty and its subdomain CF. It exposed the heterogeneity and the deviations present from their respective concepts. A simple, time efficient, universally accepted frailty operationalisation tool for use in clinical practice will simplify management of geriatric patients. It will pave the way for better allocation of healthcare resources among geriatric patients curtailing the complications and costs associated with over or under-treatment. In theory, a unifying frailty language would facilitate comparability in research and clinical practice. However, in day to day practice, this may be challenging to achieve as one frailty tool is most probably not sufficient to measure vulnerability across various geriatric subpopulations, such as, community-dwellers, geriatric in-patients, pre-op geriatric patients. Thereby, we propose that researchers/clinicians use the most appropriate frailty instrument (guided by our review) taking into consideration the setting and population subtype where frailty needs to be measured. On the other hand, the ICF may be purposeful in developing a core set (including a-ADL) related to CF. The second part of this thesis revealed that in the oldest old, prevalent RFs such as ARHL and MetS were associated with CF and thereby potential targets for intervention strategies to preserve cognitive health and decelerate the frailty-disabling cascade.
Originele taal-2English
KwalificatieDoctor of Gerontology
Toekennende instantie
  • Vrije Universiteit Brussel
Begeleider(s)/adviseur
  • Gorus, Ellen, Promotor
  • Beyer, Ingo, Co-Promotor
Datum van toekenning6 sep 2022
Plaats van publicatieBrussels
Uitgever
Gedrukte ISBN's9789461173966
StatusPublished - 2022

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