To our knowledge, this is the first cross-sectional study to evaluate the relationships between frailty and MBI, and cognition. First, we determined that frailty is common in this population, with a prevalence of 30.7%. Second, MBI was also fairly common, with a prevalence of 18.2%. Third, greater burden of frailty was associated with poorer cognition, measured using the MMSE (p=.01) and MoCA (p=.04). Fourth, compared to those without MBI, MBI+ status was associated with poorer cognition measured using the MMSE (p=.049) and MoCA (p=.01) Fifth, MBI+ status predicted higher levels of frailty (OR=3.09; 95% CI=1.29-9.41), and this signal was driven by the MBI domains of decreased motivation, affective/emotional dysregulation and social inappropriateness score (p<0.05). These results suggest that in non-dementia older adults, frailty and MBI are both common and associated with small but significant impairment in global cognition.
While the prevalence of frailty was 30.7% in all participants and 69.3% for no-frailty. The prevalence of frailty in our study was relatively high compared with previous estimates, which ranged from 11% up to 26% in community samples(51-53), and the difference may be attributed to our study design and to the fact that participants came from primary care clinics. Frailty may increase the risk of future cognitive decline and that cognitive impairment may increase the risk of frailty suggesting that cognition and frailty may interact in the cycle of age-related decline(54, 55). Our results indicated that frailty was associated with aging-related cognitive declines at-risk for the preclinical phase of neurocognitive disorders, and consistent with previous studies(11-16). In their seminal study, Solfrizzi and colleagues reported that frail older adults had a higher prevalence of cognitive impairment than those without frailty (77% vs. 54%)(56). Furthermore, components of frailty appeared to be related to pathological findings of AD and vascular dementia, supporting the idea of a possible common biological pathway between frailty and cognitive disorders(57). A previous study found that there was an increase in neurons with cellular senescence and aging of microglia, and therefore, increases in apoptosis, aggregation of protein, mitochondrial dysfunction with increased reactive oxygen species and oxidative damage to proteins and lipids, and accumulation of DNA damage(57). Accordingly, increasing frailty may be an indicator of future cognitive impairment.
The prevalence of MBI (18.2%) in our non-dementia participants was higher than that reported by Creese(33) in the PROTECT study, in which 10% of community-dwelling older adults aged 50 or over (n = 9,931) reported MBI, as captured by the MBI-C. In a clinical sample of Spanish primary care patients who validated the current cut-points, the prevalence was 5.8% in older adults with subjective complaints(27) and 14.2% in MCI(58). These estimates collectively, determined using the MBI-C, are considerably lower than previous prevalence estimated generated using the Neuropsychiatric Inventory (59) which ranged from 28-51% in a community population(60, 61), and 49-85% in a cognitive neurology clinic population(60, 62). These differences may be due to the diagnostic frame of reference of one month of symptoms captured by the Neuropsychiatric Inventory, whereas the MBI-C involves a more rigorous standard of six-month symptom duration and explicit later-life onset of symptoms, in accordance with the MBI criteria. The lower MBI frequency generated using the MBI-C reflects increased diagnostic specificity for MBI, eliminating the inclusion of transient and reactive states, by excluding false positives symptoms.
Neuropsychiatric symptoms are associated with an increased risk of cognitive deficits across the lifespan, and MBI is associated with poorer cognition cross-sectionally(33), also conferring a higher risk of cognitive decline and dementia in comparison to those without MBI(21, 63-66). In agreement with this previous evidence, we also found subtle but significant impairment in global cognition according to lower scores on both the MMSE and MoCA in patients with MBI. Indeed, the MBI-C might have significantly higher discriminatory power than the MMSE when seeking to detect early cognitive decline(47). Considering that MBI reflects the neurobehavioral axis of pre-dementia at-risk states and is a complement to the neurocognitive risk axis represented by the MCI(67), this complementary approach may increase the yield when using both cognitive and behavioral approaches to screen for early-stage neurocognitive disorders.
In this study, we found that MBI was associated with higher levels of frailty (OR=7.44; 95% CI=1.49-37.21) even after adjustment for many potential con founders, and that this signal was driven by the MBI domains of decreased motivation, affective/emotional dysregulation and social inappropriateness (p<0.05). Our findings extend the literature by describing different patterns of association of MBI and its components with frailty, a pattern not previously established. Prior studies of the link between frailty and cognition have focused on individual functional abilities and assessed only global cognitive ability or limited cognitive domains(14, 68). The mechanisms for the association are not clear, but possibly involves abnormalities in biological processes related to aging(69). A growing body of epidemiological evidence indicates that the mechanisms involved in the onset of frailty are also those that promote neurodegeneration, including chronic inflammation(54) and oxidative stress(70). Other clinical polypharmacy and multimorbidity can increase the risk of both frailty and dementia(71, 72).
MBI may serve as a proxy marker for frailty, or potentially a risk factor of frailty. Thus, MBI assessment may provide an approach to identify frailty early or to determine the risk of frailty in advance of completing a clinical assessment. This approach identifies potentially novel opportunities to prevent or delay frailty, age-related cognitive decline and other associated adverse health outcomes. The ease of administration of the MBI-C, which has even been validated for telephone administration with high sensitivity and specificity(27), positions it as a simple and cost-effective tool for detecting those at clinical risk for further assessment and work up.
The limitations of our study include the participant population and the sample size. Lower prevalence of MBI and frailty among participants in communities rather than clinical, hospital, or institutional settings are to be expected, and it is unclear if these results can be generalized. We had a limited sample size in this study, and replication with a larger sample is required. Hence, the clinical utility of the cognitive frailty construct cannot be unequivocally supported by this study, but it should be further investigated in future studies independently undertaken by other investigators in older populations.