1.3 Function in older age
1.3.5 Multimorbidity and functional decline
Apart from a few exceptions (122), the association between multimorbidity and poor physical function in older adults was demonstrated in several cross-sectional and longitudinal studies (12, 123, 124). According to a population-based study by Aarts et al., functional impairment from multimorbidity persists over time and often shows further worsening (125). Jindai et al. showed that, in older individuals, the association between multimorbidity and functional limitation is strengthened in older age (>75) and in females. If the modifier effect of older age is expected, given the reduced resilience of the oldest old individuals, the effect of the sex of the individual requires further investigation (126).
Sparse evidence suggests that, in older individuals, specific clusters of chronic disease exert a differential impact on physical function and disability (27). Some combinations of disease may be more detrimental than others in their effect on physical function as the result of mechanisms stemming from the dysfunction of various bodily systems (127, 128). Given the focus here on the health impact of cardiovascular and neuropsychiatric multimorbidity, published evidence of cardiovascular and neuropsychiatric clusters of multimorbidity and functional decline in older adults is reported. Beyond one of the constituent papers of this thesis, four studies investigated the association between multimorbidity clusters and disability. Jackson et al. reported that, in a sample of 7,270 older women participating in the Australian Longitudinal Study on Women’s Health, cardiovascular and neuropsychiatric clusters of chronic disease— but not musculoskeletal—were significantly associated with more dependence in B-ADL and I-ADL (129). Koller et al., in a study based on administrative data from 115,203 older individuals, reported a significant association between all the main multimorbidity patterns identified in the study and dependency. Notably, the cluster including neuropsychiatric diseases showed the strongest association with dependency (130). Quiñones et al., using longitudinal data from the United States on nearly 9,000 older individuals, found that the multimorbidity cluster composed of symptoms of depression, arthritis, and hypertension predicted disability better than other multimorbidity clusters (131). This result was replicated in another study based on 4,000 older adults from the Medicare database in which the copresence of physical and mental disorders (especially cognitive impairment and dementia) was linked with a higher likelihood of disability, relative to reporting several exclusively physical conditions (132). The abovementioned studies provide several insights into the association between multimorbidity clusters and function in older people. First, cardiovascular and neuropsychiatric diseases represent the most common conditions in older adults and feature as recognizable clusters of multimorbidity. Second, these two disease groups are independent predictors of poor functioning. Third, neuropsychiatric diseases show a stronger impact than cardiovascular diseases on functional outcomes. Finally, the presence of neuropsychiatric diseases seems to exacerbate the negative consequences of other individual conditions, suggesting the existence of a biological interaction among such morbidities.
However, several issues inhibit the generalizability of the results of these studies, limiting the possibility of drawing definitive conclusions about the relationship between cardiovascular and neuropsychiatric multimorbidity and functional decline. First, those studies relied on ad hoc
assessing frailty. In several clinical studies it allowed a reliable stratification of the clinical risk of specific conditions related to procedures and interventions (119-121) .
1.3.5 Multimorbidity and functional decline
Apart from a few exceptions (122), the association between multimorbidity and poor physical function in older adults was demonstrated in several cross-sectional and longitudinal studies (12, 123, 124). According to a population-based study by Aarts et al., functional impairment from multimorbidity persists over time and often shows further worsening (125). Jindai et al. showed that, in older individuals, the association between multimorbidity and functional limitation is strengthened in older age (>75) and in females. If the modifier effect of older age is expected, given the reduced resilience of the oldest old individuals, the effect of the sex of the individual requires further investigation (126).
Sparse evidence suggests that, in older individuals, specific clusters of chronic disease exert a differential impact on physical function and disability (27). Some combinations of disease may be more detrimental than others in their effect on physical function as the result of mechanisms stemming from the dysfunction of various bodily systems (127, 128). Given the focus here on the health impact of cardiovascular and neuropsychiatric multimorbidity, published evidence of cardiovascular and neuropsychiatric clusters of multimorbidity and functional decline in older adults is reported. Beyond one of the constituent papers of this thesis, four studies investigated the association between multimorbidity clusters and disability. Jackson et al. reported that, in a sample of 7,270 older women participating in the Australian Longitudinal Study on Women’s Health, cardiovascular and neuropsychiatric clusters of chronic disease— but not musculoskeletal—were significantly associated with more dependence in B-ADL and I-ADL (129). Koller et al., in a study based on administrative data from 115,203 older individuals, reported a significant association between all the main multimorbidity patterns identified in the study and dependency. Notably, the cluster including neuropsychiatric diseases showed the strongest association with dependency (130). Quiñones et al., using longitudinal data from the United States on nearly 9,000 older individuals, found that the multimorbidity cluster composed of symptoms of depression, arthritis, and hypertension predicted disability better than other multimorbidity clusters (131). This result was replicated in another study based on 4,000 older adults from the Medicare database in which the copresence of physical and mental disorders (especially cognitive impairment and dementia) was linked with a higher likelihood of disability, relative to reporting several exclusively physical conditions (132). The abovementioned studies provide several insights into the association between multimorbidity clusters and function in older people. First, cardiovascular and neuropsychiatric diseases represent the most common conditions in older adults and feature as recognizable clusters of multimorbidity. Second, these two disease groups are independent predictors of poor functioning. Third, neuropsychiatric diseases show a stronger impact than cardiovascular diseases on functional outcomes. Finally, the presence of neuropsychiatric diseases seems to exacerbate the negative consequences of other individual conditions, suggesting the existence of a biological interaction among such morbidities.
However, several issues inhibit the generalizability of the results of these studies, limiting the possibility of drawing definitive conclusions about the relationship between cardiovascular and neuropsychiatric multimorbidity and functional decline. First, those studies relied on ad hoc
and not comprehensive lists of chronic diseases. Second, the multimorbidity patterns were developed according to data-driven—not clinical—principles. Third, the dynamic and evolving nature of multimorbidity and other measures was not considered.
1.3.6 Knowledge gaps antecedent to this thesis
Despite many studies showing an independent impact of multimorbidity on several negative outcomes, some failed to demonstrate an independent association. On the one hand, this may be attributed to methodological inconsistencies in the way multimorbidity was operationalized. On the other hand, the scarce specificity implicit in the definition of multimorbidity—the co- occurrence of two or more diseases—may lead to heterogeneous and unexpected results. In this regard, reducing the heterogeneity of the exposure and assessing more homogeneous clusters of multimorbidity can help to identify groups of chronic disease selectively associated with specific outcomes.
Finally, several studies clearly showed that many older individuals are able to live a satisfying life in spite of the presence of multiple chronic diseases. Rather, the concurrent development of functional impairment is widely believed to drive the negative consequences of multimorbidity. Notably, only a handful of studies investigated the interplay between multimorbidity and functional impairment, and none of them assessed the role played by specific multimorbidity clusters. Understanding the effect of the interplay between multimorbidity and functional impairment in older adults may improve the detection of groups of individuals with more intense health-care needs and poor prognoses, in line with the principles of patient-centered care.
and not comprehensive lists of chronic diseases. Second, the multimorbidity patterns were developed according to data-driven—not clinical—principles. Third, the dynamic and evolving nature of multimorbidity and other measures was not considered.
1.3.6 Knowledge gaps antecedent to this thesis
Despite many studies showing an independent impact of multimorbidity on several negative outcomes, some failed to demonstrate an independent association. On the one hand, this may be attributed to methodological inconsistencies in the way multimorbidity was operationalized. On the other hand, the scarce specificity implicit in the definition of multimorbidity—the co- occurrence of two or more diseases—may lead to heterogeneous and unexpected results. In this regard, reducing the heterogeneity of the exposure and assessing more homogeneous clusters of multimorbidity can help to identify groups of chronic disease selectively associated with specific outcomes.
Finally, several studies clearly showed that many older individuals are able to live a satisfying life in spite of the presence of multiple chronic diseases. Rather, the concurrent development of functional impairment is widely believed to drive the negative consequences of multimorbidity. Notably, only a handful of studies investigated the interplay between multimorbidity and functional impairment, and none of them assessed the role played by specific multimorbidity clusters. Understanding the effect of the interplay between multimorbidity and functional impairment in older adults may improve the detection of groups of individuals with more intense health-care needs and poor prognoses, in line with the principles of patient-centered care.