Predicting risk of declining functional ability in community-dwelling older people.

OBJECTIVE: The frailty phenotype (FP) proposed by Fried and colleagues has been shown to be strongly associated with incident disability, but its discriminative capacities remain suboptimal, with good specificity but a sensitivity of only 10-20%. The objective of the present study was to evaluate whether the addition to the FP of other biological and social variables may improve the prediction of declining functional ability in community-dwelling older people. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Community-dwelling older subjects. METHODS: We used data from the InChianti (N 897) and the SHARE (N 444) studies to derive and validate a scoring system consisting of FP components along with age, perceived health status and markers of socio-economic disadvantage. Backward stepwise logistic regressions were used to obtain a parsimonious model, able to predict the loss of ability to perform instrumental or basic activities of daily living over time. RESULTS: A scoring system derived from a model only including age, low physical activity level, exhaustion and perceived health status had an area under the receiver operating characteristic curve (AUROC) of 0.846 in the training cohort (InChianti), and 0.745 in the testing cohort (SHARE). By applying the cut-off of 33 and 25 in the InChianti and SHARE, respectively, sensitivity raised to 0.70 and 0.62 with specificity of 0.83 and 0.70, respectively. CONCLUSIONS AND IMPLICATIONS: A simple score based on anamnestic variables may be more sensitive than the FP towards worsening functional ability, while retaining good specificity. Further studies are needed to confirm its performance.

Counting deficits or diseases? The agreement between frailty and multimorbidity in subjects with cognitive disturbances.

In the present study, we explored the relationship between multimorbidity and frailty in a population of older individuals with cognitive disturbances attending a memory clinic. All subjects consecutively attending the Memory Clinic of the Department of Human Neuroscience, "Sapienza" University of Rome, between January 2017 and April 2018 for a first neurological evaluation were considered for the present analysis. Multimorbidity was defined as the simultaneous presence of two or more diseases in the same individual. A Frailty Index was computed by considering 44 age-related, multidimensional health deficits. Overall, 185 subjects were recruited in the study. A condition of multimorbidity was detected in 87.6% of the sample, whereas only the 44.6% of the study population was considered as frail. A poor agreement was observed between multimorbidity and frailty. The present findings confirm that counting diseases or health deficits may provide discordant information concerning the risk profile of older subjects.

Race reporting and disparities in clinical trials on Alzheimer's disease: A systematic review.

INTRODUCTION: Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD). METHODS: A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications. RESULTS: Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants. DISCUSSION: Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected.

External Validity of Randomized Controlled Trials on Alzheimer's Disease: The Biases of Frailty and Biological Aging.

To date, the external validity of randomized controlled trials (RCTs) on Alzheimer's disease (AD) has been assessed only considering monodimensional variables. Nevertheless, looking at isolated and single characteristics cannot guarantee a sufficient level of appreciation of the AD patients' complexity. The only way to understand whether the two worlds (i.e., research and clinics) deal with the same type of patients is to adopt multidimensional approaches more holistically reflecting the biological age of the individual. In the present study, we compared measures of frailty/biological aging [assessed by a Frailty Index (FI)] of a sample of patients with AD resulted eligible and subsequently included in phase III RCTs compared to patients referring to the same clinical service, but not considered for inclusion. The "RCT sample" and the "real world sample" were found to be statistically similar for all the considered sociodemographic and clinical variables. Nevertheless, the "real world sample" was found to be significantly frailer compared to the "RCT sample," as indicated by higher FI scores [0.28 (SD 0.1) vs. 0.17 (SD 0.1); p < 0.001, respectively]. Moreover, when assessing the relationship between FI and age, we found that the correlation was almost null in the "RCT sample" (Spearman's r = 0.01; p = 0.98), while it was statistically significant in the "real world sample" (r = 0.49; p = 0.02). The application of too rigid designs may result in the poor representativeness of RCT samples. It may even imply the study of a condition biologically different from that observed in the "real world." The adoption of multidimensional measures capable to capture the individual's biological age may facilitate evaluating the external validity of clinical studies, implicitly improving the interpretation of the results and their translation in the clinical arena.

Sex and gender differences in the treatment of Alzheimer's disease: A systematic review of randomized controlled trials.

In recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influence of sex and gender on Alzheimer's disease (AD). Nevertheless, not enough attention has been paid to their impact on treatment outcomes. The present study is aimed at systematically retrieve, review and discuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketed treatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possible sex and gender differences in their efficacy, safety and tolerability. A systematic review of literature was performed. None of the retrieved studies reported data on the efficacy, safety and tolerability of considered medications separately in male and female patients with AD. We thus analyzed 48 excluded studies of potential interest, that is, almost all of the currently available trials on the four considered drugs. Nearly all the considered RCTs recruited a larger number of female participants to mirror the sexually unbalanced prevalence of AD. Only two studies took into account the potential influence of sex and gender on treatment efficacy, reporting no significant differences between men and women. None of the studies investigated potential sex and gender differences in the safety and tolerability of the four considered treatments. The existence of sex and gender differences in the efficacy and tolerability of ChEIs and memantine in AD has, to date, drawn limited to no attention. However, a considerable amount of data, with an adequate representativeness in terms of sex/gender distribution, seem to be already available for dedicated analyses on this topic. A greater effort should be made to collect and report data on those factors interacting with sex and gender that may significantly influence clinical manifestations, outcomes, and trajectories over time of AD patients.

Nutrition and Dementia: Evidence for Preventive Approaches?

In recent years, the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship between nutritional habits and cognitive health has attracted special attention. The present review is designed to retrieve and discuss recent evidence (published over the last 3 years) coming from randomized controlled trials (RCTs) investigating the efficacy of nutritional interventions aimed at improving cognitive functioning and/or preventing cognitive decline in non-demented older individuals. A systematic review of literature was conducted, leading to the identification of 11 studies of interest. Overall, most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits (defined as improved neuropsychological test scores). Nevertheless, the clinical meaningfulness of such findings was not adequately discussed and appears controversial. In parallel, only 2 studies investigated between-group differences concerning incident dementia and mild cognitive impairment cases, reporting conflicting results. Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing, slowing, and preventing cognitive decline. However, supporting evidence is overall weak and further studies are needed.