Development of a clinical prediction model for the onset of functional decline in people aged 65-75 years: Pooled analysis of four European cohort studies

Background: Identifying those people at increased risk of early functional decline in activities of daily living (ADL) is essential for initiating preventive interventions. The aim of this study is to develop and validate a clinical prediction model for onset of functional decline in ADL in three years of follow-up in older people of 65-75 years old. Methods: Four population-based cohort studies were pooled for the analysis: ActiFE-ULM (Germany), ELSA (United Kingdom), InCHIANTI (Italy), LASA (Netherlands). Included participants were 65-75 years old at baseline and reported no limitations in functional ability in ADL at baseline. Functional decline was assessed with two items on basic ADL and three items on instrumental ADL. Participants who reported at least some limitations at three-year follow-up on any of the five items were classified as experiencing functional decline. Multiple logistic regression analysis was used to develop a prediction model, with subsequent bootstrapping for optimism-correction. We applied internal-external cross-validation by alternating the data from the four cohort studies to assess the discrimination and calibration across the cohorts. Results: Two thousand five hundred sixty community-dwelling people were included in the analyses (mean age 69.7 ± 3.0 years old, 47.4% female) of whom 572 (22.3%) reported functional decline at three-year follow-up. The final prediction model included 10 out of 22 predictors: age, handgrip strength, gait speed, five-repeated chair stands time (non-linear association), body mass index, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, arthritis, and depressive symptoms. The optimism-corrected model showed good discrimination with a C statistic of 0.72. The calibration intercept was 0.06 and the calibration slope was 1.05. Internal-external cross-validation showed consistent performance of the model across the four cohorts. Conclusions: Based on pooled cohort data analyses we were able to show that the onset of functional decline in ADL in three years in older people aged 65-75 years can be predicted by specific physical performance measures, age, body mass index, presence of depressive symptoms, and chronic conditions. The prediction model showed good discrimination and calibration, which remained stable across the four cohorts, supporting external validity of our findings

Physical Activity as Moderator of the Association Between APOE and Cognitive Decline in Older Adults: Results from Three Longitudinal Cohort Studies

Background: Previous studies have suggested that the association between APOE ɛ4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline are missing. In this study, we examine whether there is a gene– environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies. Methods: We followed 7,176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI, and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate, and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of three points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using generalized estimating equations adjusting for age, sex, education, depressive symptoms, and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale. Results: Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ4 carriers had higher odds of cognitive decline (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.29–1.64) while PA was not significantly associated with cognitive decline overall (moderate PA: OR = 0.87, 0.67–1.13; high PA: OR = 0.71, 0.36–1.40). There was no evidence for an interaction effect between PA and APOE ɛ4 in cognitive decline in older adults (APOE × moderate PA: p = .83; APOE × high PA: p = .90). Conclusions: Previous claims of a gene–environment interaction between APOE ɛ4 and PA in cognitive decline are not supported by our results

Instability, investment, disasters, and demography: natural disasters and fertility in Italy (1820–1962) and Japan (1671–1965)

This article examines whether natural disasters affect fertility—a topic little explored but of policy importance given relevance to policies regarding disaster insurance, foreign aid, and the environment. The identification strategy uses historic regional data to exploit natural variation within each of two countries: one European country—Italy (1820–1962), and one Asian country—Japan (1671–1965). The choice of study settings allows consideration of Jones’ (The European miracle, Cambridge University Press, Cambridge, 1981) theory that preindustrial differences in income and population between Asia and Europe resulted from the fertility response to different environmental risk profiles. According to the results, short-run instability, particularly that arising from the natural environment, appears to be associated with a decrease in fertility—thereby suggesting that environmental shocks and economic volatility are associated with a decrease in investment in the population size of future generations. The results also show that, contrary to Jones’ (The European miracle, Cambridge University Press, Cambridge, 1981) theory, differences in fertility between Italy and Japan cannot be explained away by disaster proneness alone. Research on the effects of natural disasters may enable social scientists and environmentalists alike to better predict the potential effects of the increase in natural disasters that may result from global climate change

Predicting trajectories of functional decline in 60- to 70-year-old people

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions. Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60–70 years. Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60–70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0–1). Participants were included if they reported data on ≥ 2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex. Results: Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57–0.97; severe limitations, OR 0.42, 95% CI 0.26–0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62–0.73; intermediate decline, AUC 0.63, 95% CI 0.56–0.69; severe decline, AUC 0.79, 95% CI 0.71–0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38–0.68) and severe limitations (OR 0.18, 95% CI 0.07–0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75–0.85; intermediate decline, AUC 0.74, 95% CI 0.69–0.79; severe decline, AUC 0.95, 95% CI 0.91–0.99). Conclusion: Already in people aged 60–70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions

Supplementary Material for: Predicting Trajectories of Functional Decline in 60- to 70-Year-Old People

<p><b><i>Background:</i></b> Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions. <b><i>Objective:</i></b> The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years. <b><i>Methods:</i></b> We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1). Participants were included if they reported data on ≥2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex. <b><i>Results:</i></b> Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57-0.97; severe limitations, OR 0.42, 95% CI 0.26-0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62-0.73; intermediate decline, AUC 0.63, 95% CI 0.56-0.69; severe decline, AUC 0.79, 95% CI 0.71-0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38-0.68) and severe limitations (OR 0.18, 95% CI 0.07-0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75-0.85; intermediate decline, AUC 0.74, 95% CI 0.69-0.79; severe decline, AUC 0.95, 95% CI 0.91-0.99). <b><i>Conclusion:</i></b> Already in people aged 60-70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions.</p

MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events.

MUTYH-associated polyposis (MAP) is an autosomal recessive adenomatous polyposis caused by biallelic germline mutations of the base-excision-repair gene MUTYH. In MAP patients of European origin, the combined allele frequency of the mutations p.Tyr179Cys and p.Gly396Asp ranges between 50 and 82%, while these mutations have not been identified in Far Eastern Asian populations, supporting the hypothesis that a founder effect has occurred at some point in European history. To investigate the natural history of the two common European MUTYH alleles, we genotyped six gene-flanking microsatellite markers in 80 unrelated Italian and German MAP patients segregating one or both mutations and calculated their age in generations (g) by using DMLE+2.2 software. Three distinct common haplotypes, one for p.Tyr179Cys and two for p.Gly396Asp, were identified. Estimated mutation ages were 305\u2009g (95% CS: 271-418) for p.Tyr179Cys and 350\u2009g (95% CS: 313-435) for p.Gly396Asp. These results provide evidence for strong founder effects and suggest that the p.Tyr179Cys and p.Gly396Asp mutations derive from ancestors who lived between 5-8 thousand years and 6-9 thousand years B.C., respectivel