The Impact of Frailty on the Risk of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: Evidences from a 5-Year Observational Study

Abstract

The frailty construct has increasingly been adopted in the field of cognitive disorders. The aim of the present study was to measure frailty in a cohort of individuals with mild cognitive impairment (MCI) and to explore whether frailty measures may consent to predict the risk of conversion to dementia. We retrospectively reviewed the clinical charts of outpatients with amnesic MCI (aMCI) consecutively recruited at our Department, and followed-up for 5 years. Individual frailty status was measured by means of a frailty index (FI) consisting of 39 deficits (including signs, symptoms, diagnoses, and disabilities). Univariate analyses were used to compare the socio-demographic and clinical characteristics between subjects converting or not converting to probable Alzheimer’s disease (AD) dementia over the follow-up. Risk for conversion to AD dementia was assessed using Cox regression models. Ninety-one subjects with aMCI (mean age 72.7, SD 7.1 years; women 49.5%) were consecutively recruited over a period of 12 months. Low levels of frailty were documented in the sample (mean FI score 10.0, SD 5.3). A statistically significant correlation between age and FI was observed. Overall, 58 participants converted to AD dementia over time. The Cox regression analysis showed that age (HR: 1.04, 95% CI: 1.00–1.08), male sex (HR: 0.52, 95% CI: 0.30–0.91), Mini–Mental State Examination score (HR: 0.85, 95% CI: 0.77–0.94), and FI (HR: 1.11, 95% CI: 1.05–1.18) were all significantly associated with the probability of MCI conversion. Individual’s frailty status may increase the risk of conversion from a condition of MCI to overt AD dementia. The adoption of constructs comprehensively reflecting the biological decline of the aging subject may add useful estimates and information in the clinical approach to cognitive disorders.

Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of Alzheimer’s Disease

“…It is not clear whether sex differences in mortality in mouse models of AD indicate sex-specific phenotypes, or differences in survival in response to the same degree of pathology. The sex differences in mortality in AD mouse models appears to correspond to what is seen in humans; men with AD generally have greater mortality risk than women (Sinforiani et al, 2010 ; Mielke et al, 2014 ; Mazure and Swendsen, 2016 ) and have a higher FI (Trebbastoni et al, 2017 ). In humans, the mechanism underlying this sex difference in lifespan is not well understood but may be related to sex differences in brain development and structure, in risk factors for AD (Mielke et al, 2014 ), or in the pathology of AD (Mielke et al, 2014 ; Mazure and Swendsen, 2016 ).…”

“…In terms of frailty, women have higher FI scores than men at all ages, but, paradoxically, have lower mortality risk (Mitnitski et al, 2002 ; Puts et al, 2005 ; Yang and Lee, 2010 ; Gordon et al, 2017 ). The FI is also related to cognitive decline in Alzheimer’s patients as increases in the FI are correlated with increased cognitive decline and a higher probability of converting from mild cognitive impairment (MCI) to AD (Kelaiditi et al, 2016 ; Trebbastoni et al, 2017 ). Increasing age, male sex and higher FI scores were associated with a higher probability of converting from MCI to AD in patients (Trebbastoni et al, 2017 ).…”

Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation

“…A more rapid rate of increasing frailty is related to a more rapid loss of cognitive functions and low response to therapy [ 89 , 90 ]. Frailty level correlates with AD biomarkers [ 91 ] and the higher probability for mild cognitive impairment (MCI) to progress to AD [ 92 , 93 ]. We have recently suggested that frailty status could be a useful marker in preclinical assessment of novel AD therapeutics [ 52 ].…”

Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia

“…[11][12][13] Measuring each individual's degree of frailty may help identify those individuals without cognitive impairment most likely to develop MCI, 14 and those with MCI most likely to progress to dementia. 15 Critically, despite recent recommendations in support of preventing and mitigating frailty 16 -chiefly through lifestyle interventions that overlap with those proposed for dementia-it is not yet known whether frailty plays an equal role in dementia development in relation to a genetic predisposition to dementia. Recent evidence is mixed about whether a healthy lifestyle reduces dementia risk in those at high genetic risk.…”