HG - SR.2019.09.01. Trayectorias de Envejecimiento Humano en México

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OPEN Healthy ageing trajectories and


lifestyle behaviour: the Mexican
Health and Aging Study
Received: 5 October 2018 Christina Daskalopoulou   1, Artemis Koukounari2, Yu-Tzu Wu1, Graciela Muniz Terrera3,
Accepted: 12 July 2019 Francisco Félix Caballero4,5, Javier de la Fuente6,7, Stefanos Tyrovolas8,9,
Published: xx xx xxxx Demosthenes B. Panagiotakos   10, Martin Prince1 & Matthew Prina1
Projections show that the number of people above 60 years old will triple by 2050 in Mexico.
Nevertheless, ageing is characterised by great variability in the health status. In this study, we aimed
to identify trajectories of health and their associations with lifestyle factors in a national representative
cohort study of older Mexicans. We used secondary data of 14,143 adults from the Mexican Health
and Aging Study (MHAS). A metric of health, based on the conceptual framework of functional ability,
was mapped onto four waves (2001, 2003, 2012, 2015) and created by applying Bayesian multilevel
Item Response Theory (IRT). Conditional Growth Mixture Modelling (GMM) was used to identify latent
classes of individuals with similar trajectories and examine the impact of physical activity, smoking
and alcohol on those. Conditional on sociodemographic and lifestyle behaviour four latent classes were
suggested: high-stable, moderate-stable, low-stable and decliners. Participants who did not engage in
physical activity, were current or previous smokers and did not consume alcohol at baseline were more
likely to be in the trajectory with the highest deterioration (i.e. decliners). This study confirms ageing
heterogeneity and the positive influence of a healthy lifestyle. These results provide the ground for new
policies.

The number of people 60 years old and over is increasing and many parts of the world will experience a significant
growth in the next decades1. An increased life expectancy is the result of medical and technological advances
together with better social and environmental conditions. However, living longer does not entail that these added
years will be spent in good health as there is contradictory evidence that older people nowadays age with better
health compared to their parents2,3. Furthermore, population ageing has been associated with an increased risk of
non-communicable diseases4, disability5 and frailty6. All these put extra challenges on the already stretched public
health and social care sectors.
Reviews indicated that many studies have examined various factors which influence the health of older peo-
ple in a positive or a negative way7,8. However, the vast majority of research has assumed that a single ageing
profile, in which good health is followed by rapid decline and then death, is representative of all older people.
Nevertheless, recent findings suggest that ageing is a heterogeneous process and that no typical ageing profile
exists9. To be able to provide valuable insight to policymakers and clinicians on the various ageing profiles, there
is a need to identify those factors that have the largest effect on the interindividual heterogeneity of getting older.
Furthermore, identifying the interrelationships of risk factors with the various ageing pathways could contribute

1
Department of Health Service and Population Research, King’s College London, Institute of Psychiatry, Psychology
and Neuroscience, London, UK. 2Department of Infectious Disease Epidemiology, London School of Hygiene &
Tropical Medicine, Faculty of Epidemiology and Population Health, London, UK. 3Centre for Dementia Prevention,
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. 4Department of Preventive Medicine and
Public Health and Microbiology, Universidad Autónoma de Madrid, Madrid, Spain. 5Ciber of Epidemiology and Public
Health, Carlos III Institute of Health, Madrid, Spain. 6Hospital Universitario de La Princesa, Instituto de Investigación
Sanitaria Princesa (IIS Princesa), Madrid, Spain. 7Department of Psychiatry, Universidad Autónoma de Madrid,
Madrid, Spain. 8Parc Sanitari Sant Joan de Déu, Universitat de Barcelona. Fundació Sant Joan de Déu, Dr Antoni
Pujades, 42, 08830, Sant Boi de Llobregat, Barcelona, Spain. 9Instituto de Salud Carlos III, Centro de Investigación
Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain. 10Department of Nutrition and Dietetics, School of
Health Science and Education, Harokopio University, Athens, Greece. Correspondence and requests for materials
should be addressed to C.D. (email: [email protected])

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to more targeted strategies, and hence more effective, that could enable people to prevent or control any negative
health outcomes.
Even though population ageing is a global phenomenon, areas of the world have been experiencing a different
demographic transition. Latin American countries and the Caribbean figure among those that are projected to
experience the fastest population growth in the following decades1. Population ageing in Mexico has been charac-
terised as America’s big challenge as the proportion of people above 65 years old is projected to triple by 205010. In
addition, in Mexico the epidemiological transition from communicable diseases to non-communicable diseases
has been linked with an unprecedented increased risk of non-chronic diseases (i.e. diabetes, chronic kidney dis-
ease)11. However, ageing research in Mexico is very limited; especially, with regards to the different ageing profiles
and their associations with protective or risk factors8. Recent systematic reviews highlight the positive effect of
modifiable lifestyle factors, in particular physical activity and smoking abstinence, on healthy ageing12,13. Yet, in
Mexico smoking continues to be a serious public health problem and one of the most important risk factors of
diseases and mortality14. In addition the proportion of people being physically inactive, especially among older
Mexicans, has been increased during the last years15. An increase in the detrimental use of alcohol consumption,
mainly binge drinking, has also been observed lately16.
The purpose of this study was to identify subgroups of older Mexicans exhibiting similar health trajectories
over the later years of the life course and to examine the effect of physical activity, non-smoking and alcohol
consumption on those across 14 years of follow-up. In our study, health in older people was conceptualised
within the functional ability framework as suggested by the latest report of Health and Ageing from the World
Health Organisation (WHO). More specifically, WHO defined healthy ageing as “the process of developing and
maintaining the functional ability that enables older people to do the things that matter to them”17. Functional
ability is comprised by the intrinsic capacity of an individual, physical and mental capacities, and the surrounding
environment (i.e. community, home, devices). Within this framework, more focus is based on function than the
presence of any disease or comorbidity18.

Design and Methods


Study sample.  The Mexican Health and Aging Study (MHAS) is the first urban-rural nationally repre-
sentative longitudinal study of older adults in Mexico. The main goal of the MHAS was to examine the ageing
process and the disease and disability burden of people 50 years old and over from various socioeconomic back-
grounds19,20. The study protocol and instruments were approved by the Institutional Review Board or Ethics
Committee of the University of Texas Medical Branch, the INEGI and the Instituto Nacional de Salud Pública in
Mexico. Freely accessible datasets and detailed documentation are provided (www.MHASweb.org).
The baseline survey took place in 2001 and there are three follow-up waves available; 2003, 2012 and 2015.
Data were obtained from face-to-face interviews and in case where the participant was absent or in poor health,
proxy interviews took place. For the needs of the current study, we considered data from direct interviews of par-
ticipants who were firstly interviewed in 2001 and then followed-up. We did not include participants who were
firstly interviewed in a follow-up wave.

Indicators of health.  In this study, to conceptualise health in older age, we adopted the functional ability
framework as provided by WHO17. Items of functional ability and measured tests were identified in the 4 waves
to create a metric of health status in old age. A set of 40 items providing information on difficulties of activities of
daily living (ADLs) and on instrumental activities of daily living (iADLs), together with items measuring pain,
sleep and energy problems, and cognitive tests were identified in the 4 waves. 30 items were available in all waves
and constitute the anchor items (i.e. items contributing to parameters linkage) (Supplementary Table S1). To cre-
ate the health metric, we included items available in all waves and items measured in at least 2 waves.
Answers to the items were recoded to define presence or absence of the difficulty, items with adverse coding
were recoded accordingly. Participants who refused or declined to answer a question were handled as missing
cases (less than 1% on average in the 4 waves); responses from participants who answered “cannot do the activ-
ity” were recoded as “having the difficulty” whereas responses from participants who answered “do not do the
activity” were recorded as “not having the difficulty”. Hearing and eyesight condition were recoded as good when
participants replied excellent, very good, good or fair and poor when they replied poor or worse. In our study ver-
bal fluency was examined by the number of animals remembered in one minute; participants with values ≤ 25th
percentile were characterised as having low ability.

Covariates.  In our models we considered age, sex, educational level, physical activity, smoking and alcohol
consumption as covariates. Educational level was grouped as ‘none, primary, secondary, technical or commercial,
preparatory or high school, basic teaching school, college, and graduate’ with higher values indicating higher
level. Physical activity was captured via a single question asking participants if on average during the last 2 years
they had exercised or done hard physical work 3 or more times a week, including various activities such as sports,
heavy household chores, or other physical work. Smoking history was assessed by a single question asking if the
individual had smoked more than 100 cigarettes or 5 packs in his lifetime. Alcohol history was assessed in a sim-
ilar way by asking participants if ever drink alcoholic beverages.

Analytical Procedure
Health metric.  To fully capture the underlying latent construct of health in older age, we created a measure-
ment model. The measurement model includes parameters that represent the difficulty and the discriminatory
power of each question/ item. By this approach, items are allowed to differ in their relative difficulty and discrim-
ination ability. Thus, we are able to differentiate participants with similar levels of health. More specifically, to
create a common metric of health we employed Bayesian multilevel Item Response Theory (IRT) and estimated a

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two parameter normal-ogive model21. Item parameters (difficulty and discrimination) determine the exact rela-
tionship between the latent trait and the probability of the response to a particular item22. The IRT model assumes
a one-dimensional continuous latent variable (in our study the health trait) that predicts the probability of a
certain observed response to each item.
A random item effects (multilevel) approach was implemented to take into account the multilevel structure of
the data and allow item parameters to vary across waves. By this approach wave-specific parameters are assumed
to follow a normal distribution: bij~N(bi, σb,i2), aij~N(ai, σa,i2) (b: difficulty; a: discrimination; σ: standard devia-
tion; i: item; j: wave) and to be random deviations from the overall item “hyperparameters”23. In a multilevel IRT
model, a “hierarchical prior distribution or hyperprior” can also be assumed for the hyperparameters: bi~N(μσ,
ωb2); ai~N(1, ωa2). The Bayesian framework was adopted as it allows to simultaneously estimate all parameters
under a Markov Chain Monte Carlo (MCMC) estimation method and to also include different sets of items per
wave24.
We compared 4 potential models according to the estimated variance components in the item parameters
across the 4 waves: (1) no variance in the difficulty and discrimination parameters (σb,i2 and σa,i2 were assumed to
be zero); (2) item-specific difficulty variance and no variance in the discrimination parameters (σb,i2 is estimated);
(3) homogeneous difficulty variance and no discrimination variance (a joint variance of all item difficulties is
estimated σb,12 = σb,22 = … = σb,I2); (4) variance in difficulty and discrimination parameters and estimation of the
hyperprior distribution (σb,i2 and σa,i2 are estimated and hyperpriors with parameters μσ, ωb, ωa). In models (1),
(2) and (3) the discrimination parameters (aij) were fixed at one. For identification purposes, in all models and for
each wave the sum of all difficulty parameters (bi) was fixed to zero and the product of all discrimination param-
eters (ai) was fixed to one25. More information regarding the technical settings of the model and the priors of the
parameters are available in the sirt package documentation26,27 in R 3.5.1 statistical software28. 7,000 samples were
used for parameter estimation and the first 100 samples were discarded (burn-out).
To identify the model that provided the best fit in our data we examined the Expected-A-Posteriori (EAP)
estimation reliability, the Deviance information criterion (DIC), the precision of the measurement and the R-hat
MCMC convergence statistic. Higher values in EAP reliability indicate a higher reliability of the metric whereas
lower values in DIC indicate a model which is better supported by the data29. The measurement precision is
considered appropriate when the standard errors (SE) are below 0.5 for most of the spectrum of the latent con-
struct30. Finally, R-hat values substantially above 1 indicate lack of convergence for the MCMC algorithm31. The
final extracted health metric score was transformed in a scale 0–100 with higher scores indicating better health.
IRT models assume unidimensionality of the latent construct22. We investigated this assumption by per-
forming exploratory factor analysis (EFA) on a sub-sample of the initial baseline sample (70%) under a goemin
(oblique) rotation. A second-order confirmatory factor analysis (CFA) was subsequently performed on the
validation sub-sample (30%) to confirm or not that health could be represented as a single general construct.
Analyses were performed in Mplus v8.032 with the mean and variance-adjusted weighted least-squares (WLSMV)
estimator and a pairwise present approach to missing data33. To conclude about the goodness-of-fit of the models,
we examined the comparative fit index (CFI) and the root mean square of approximation (RMSEA) with 90%
confidence intervals (CI). We considered a model to have an acceptable fit when CFI ≥ 0.90 and RMSEA values
close or less than 0.0634.
Finally, to confirm the predictive validity of the health metric, we performed a Receiver Operating
Characteristics (ROC) curve analysis adjusted per gender. Mortality was assumed as the gold-standard measure
and we examined the associations of the baseline metric (2001) with mortality observed over increasing periods
of time such as: 2 years (2003), 11 years (2012) and 14 years (2015) by calculating the Area Under the ROC Curve
(AUC). ROC analyses were implemented in STATA35.

Trajectories of health.  We used growth mixture modelling (GMM) to investigate the longitudinal trajec-
tory of unobserved groups (latent classes) with similar patterns of health in older age36. By this approach, we
can identify ‘mixtures” of two or more homogeneous subpopulations in the total population37. GMM provides
information regarding the optimal number of classes, the number of people in each class, predictors of class
membership as well as the growth factors of each different trajectory. Growth factors usually entail the intercept
and the slope; the level of outcome variable when time is equal to zero and the rate of change in the outcome over
time, respectively (interpretation is also dependable on the way the model has been parameterised).
In agreement with current recommendations36, we initially performed a single-group analysis to determine
the pattern of change over time. The number of available time points (i.e. 4 waves) allowed us to examine a linear,
a latent basis and a quadratic pattern of change38. We then applied a conditional GMM (i.e. we included the covar-
iates as previously described) with a distal outcome approach to identify latent classes in terms of their health
trajectories within our dataset39. We employed an exploratory approach and we fitted models with an increasing
number of classes to identify the optimal latent class model. We also investigated several sets of models in which
we allowed for the mean, variances and/or covariance of the intercepts and slopes to differ among latent classes.
Missing data were assumed to be missing at random (MAR) and listwise deletion was applied to cases that had
missing values on covariates.
To estimate the number of latent classes, we followed recommended approaches including the comparison of
various model fit statistics, substantive meaning and interpretability of each class39. We inspected the Bayesian
information criterion (BIC), the sample-size adjusted BIC (SSABIC), entropy values and the Lo-Mendel-Rubin
likelihood ratio test (LMR-LRT)40. Lower BIC and SSABIC values indicate a more parsimonious and better fit-
ting model, whereas higher entropy values signal better class separation41. Sample size of the smallest class was
also considered42. Models were estimated in Mplus v8.0 by full maximum likelihood (FML) and robust standard
errors (MLR) to non-normality and non-independence of observations32. To avoid local maxima for the EM
(expectation-maximization) algorithm, we estimated the models with 250 random starting values.

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ε1 ε2 ε3 ε4

Health Health Health Health


metric 2001 metric 2003 metric 2012 metric 2015

Latent connuous growth variables


Intercept and Slope

Covariates
Class 1
Gender, age,
Class 2 Distal outcome
educaon level,
Class 3 death in 2015
physical acvity,

smoking, drinking

Figure 1.  General diagram of the conditional growth mixture model used in the study. Squares represent
observed variables; circles represent latent (unobserved) variables or factors; ε (epsilon) represents the
measurement error; classes represent the various unobserved groups of individuals with similar patterns of
health; the distal outcome -observed mortality status in 2015- indicates the predictive value of the health metric.

Variables Baseline 14,143


Mean-SD 59.99 (10.66)
Age
Missing 28 (0.2%)
Males 5,920 (41.9%)
Sex Females 8,195 (57.9%)
Missing 28 (0.2%)
None 3,325 (23.5%)
Primary 7,527 (53.2%)
Education Level
Above secondary 3,282 (23.2%)
Missing 9 (0.1%)
Yes 4,765 (33.7%)
Physical Activity No 9,264 (65.5%)
Missing 114 (0.8%)
Yes 6,041 (42.7%)
Ever smoked No 8,099 (57.3%)
Missing 3 (0.02%)
Yes 4,420 (31.3%)
No 8,332 (58.9%)
Drinking alcohol
Never has used alcohol 1,385 (9.8%)
Missing 6 (0.04%)

Table 1.  Descriptive statistics for the baseline wave (2001). Notes: SD: standard deviation.

It has to be pointed out that we applied a conditional GMM and investigated how classes are influenced and
predicted by the covariates. We opted for a one-step approach examining the association between latent class vari-
able and covariates to avoid estimation errors occurring when participants are forced to be classified in one-single
class43. Age, sex, education level, physical activity, smoking and alcohol consumption were simultaneously
included as covariates on the intercept and slope, and as markers of class membership. By this way, the different
associations of each covariate with the latent classes was assessed, controlling for all other covariates. Since the
latent classes are categorical, the estimated associations are from a multinomial logistic regression. Consequently,
the estimates represent the log odds of being in a non-reference latent class versus being in the reference. We also
considered mortality status in 2015 (dead or alive) as a distal outcome of the latent classes to more clearly indicate
the predictive value of the trajectories44. The model implemented is depicted in Fig. 1.

Results
Table 1 provides baseline descriptive statistics of the participants. Our sample comprised 14,143 individuals in the
baseline (5,920 men, 8,195 women) with a mean age of 59.99 (SD:10.66); the majority had at least above primary
level education (76.4%). Almost one-third of them (33.7%) reported that they had done some physical activity
within the last 2 years more than 3 times per week and that they drink alcohol beverages (31.3%). Individuals
were fairly divided in ever smokers (42.7%) and non-smokers (57.3%). Missing values on the covariates were
trivial (<0.8%).

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72

70

68

Health metric score


66

64

62

60

58
2001 2003 2012 2015
Year

Figure 2.  Health metric scores per measurement year (2001, 2003, 2012, 2015). Diamond markers represent
mean values of the health metric score; dash markers represent the upper and lower bound of the 95%
confidence interval for the mean value.

Fit Statistics 2 Classes 3 Classes 4 Classes 5 Classes 6 Classes


LL (N) −166,428.21 (46) −166,037.18 (68) −165,836.24 (90) −165,739.89 (112) n/a
BIC 333,295.53 332,723.48 332,531.61 332,548.93
SSABIC 333,149.34 332,507.38 332,245.60 332,193.00
Entropy 0.746 0.760 0.710 0.578
Adj. LMR-LRT −168,423.35* −166,428.21* −166,037.18* −165,836.24*
Group size (%) C1 26.9% 68.9% 22.6% 32.9%
C2 73.1% 23.7% 13.0% 4.7%
C3 7.4% 59.0% 10.7%
C4 5.4% 20.9%
C5 30.9%

Table 2.  Model Selection Criteria of the Growth Mixture Model (GMM) analysis. Notes: LL: Log Likelihood;
N: number of parameters; BIC: Bayesian Information Criterion; SSABIC: Sample size adjusted Bayesian
Information Criterion, Adj. LMR-LRT: adjusted likelihood ratio test; n/a: no convergence; *p-value < 0.05.

Health metric.  To estimate health in older age, model fit diagnostics concluded that the best fit model in
our dataset was Model 3, which allowed a homogeneous variance across waves for the difficulty parameter to
be estimated (Supplementary Tables S2–S6). According to the difficulty parameters of the IRT model the most
difficult items were those referring to mental abilities (i.e. visual recall, learning ability) and the least difficult were
items of iADL (i.e. difficulty eating or taking medications due to health problem). The EFA results indicated that
a four-factors model was the best solution to the latent structure of our dataset (χ2: 4,985.58, df: 402, RMSEA:
0.034; 90%CI: 0.033–0.035, CFI: 0.977); however intercorrelations among the first-order factors provided support
for a higher-order factor (Supplementary Table S7). The second-order CFA in the 30% sub-sample confirmed that
a general factor, comprised by the initial four factors of the EFA, underlies the data (χ2: 3,413.5, df: 491, RMSEA:
0.037; 90%CI: 0.036–0.039, CFI: 0.964) providing enough evidence for unidimensionality. Regarding mortality,
29% (n = 4,033) of the baseline sample was dead by 2015, 65% (n = 9,223) were found alive and no information
was available for 6% (n = 887). The gender-adjusted AUC associated with the baseline (2001) health metric for the
2003, 2012 and 2015 mortality assessments was: AUC: 0.75 (95%CI: 0.73–0.78); AUC: 0.71 (95%CI: 0.69–0.72);
AUC: 0.70 (95%CI: 0.69–0.71), respectively. The health score indicated a decreasing trend across the four waves
Fig. 2.

Trajectories of health.  To ensure that we identified the model of change that best represented the four
waves of data, we conducted three single-group analyses. These showed that the latent basis model was the most
appropriate to model the shape of change over time (lowest BIC/ SSABIC values) (Supplementary Table S8). A
final sample of 13,988 participants (out of the initial 14,143) was included in our conditional GMM analyses due
to missing data on covariates. The lowest covariance coverage for each pair of variables was 0.45 (obtained using
Mplus). Hence the missing values were within acceptable limits for the analyses (minimum threshold for model
convergence is 0.10). As noted in our analytical procedure, we examined various sets of models regarding the
means, variances and covariances of the growth factors across the latent classes. However, due to identification
and convergence reasons, we proceeded by assuming equal intercept and slope variances among latent classes.
Table 2 provides the BIC, SSABIC, entropy values and the adjusted LRT results for the one-, two-, three-, four-
and five-classes models. The four-class model was selected according to the BIC/SSABIC indexes and in com-
bination with the entropy and the adjusted LRT. This model had the lowest BIC and even thought the adjusted

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80

70

Health metric score


60

50

40

30

20

10
2001 2003 2012 2015
Years

Figure 3.  Trajectories of the conditional 4-class model. Diamond markers represent the estimated mean health
score per group across the four measurement waves (years 2001, 2003, 2012, 2015). Dash markers represent the
upper and lower bound of the 95% confidence interval for the mean values. Red points represent the decliners
group (n = 3.161); yellow points represent the low-stable group (n = 756); blue points represent the moderate-
stable group (n = 1.824) and green points represent the high-stable group (n = 8.247).

LRT and SSABIC suggested as best the five latent class model, the considerable drop of the entropy (0.58) and the
low-size classes (<5% of the total sample) indicated as better the former. Between the three and four-class models,
we proceeded with the latter as LRT indicated.
Figure 3 provides the trajectories for the latent classes in the four-classes conditional model. Based on the
growth factors, the first class (red) was named “decliners” group. There were 3,161 individuals (22.6% of the sam-
ple) with an average baseline health score of 68.27 (SE:0.40) and a steep average decline rate of −28.29 (SE:1.31)
in the follow-up waves. The second class (blue) named “moderate-stable” had 1,824 individuals (13.0%) with
moderate level of health in baseline (intercept:56.39, SE:1.31) and moderate decline (slope:-7.71, SE:1.36). The
largest class (class 3-green) called “high-stable” had 8,247 participants (59% of the sample). In this group, there
were those with high average baseline health score (intercept:75.83, SE:0.29) and moderate average rate of decline
-11.52 (SE:0.31). The smallest class (class 4-yellow) named “low-stable” had 756 participants who demonstrated
low average baseline scores (intercept:39.69, SE:1.32) and no significant average rate of change (slope:-6.46,
SE:6.94) in the follow-up waves. Decliners and low-stable groups showed the highest death probability in 2015;
0.81 (SE:0.02) and 0.95 (SE:0.03), respectively. The moderate-stable group showed a moderate death probabil-
ity after 14 years of follow-up 0.26 (SE:0.04), whereas the high-stable had the smallest death probability 0.05
(SE:0.01).

Covariates.  Lifestyle behaviour as predictors of class membership. Table 3 shows the logit coefficients as well
as the odds ratios from the multinomial logistic regression of the latent classes on the lifestyle behaviour factors
adjusted for socio-demographics. With high-stable group as the reference class, membership in the decliners and
in the low-stable group was associated with physical activity, smoking and alcohol consumption. Non-physically
active participants had greater odds of being in the decliners group (OR:1.39; 95%CI:1.17–1.66) and even greater
(OR:8.76; 95%CI:3.92–19.56) in the low-stable group compared to the high-stable group. On the contrary,
non-smokers had decreased odds of being in the decliners (OR:0.68; 95%CI:0.57–0.81) or in the low-stable group
(OR:0.56; 95%CI:0.38–0.83) compared to the high-stable group than individuals who were current or former
smokers. Non-drinkers had also increased odds of being in the decliners or in the low-stable group (OR:1.21;
95%CI:1.05–1.39, OR:1.62; 95%CI:1.14–2.30, respectively) compared to the high-stable group. Membership in
the moderate-stable group was not significantly associated with any of the examined lifestyle behaviours.

Lifestyle behaviour as predictors of growth factors.  Supplementary Table S9 presents the coefficients for the
regression of each class specific growth factors on the lifestyle factors adjusted for socio-demographics. Only
physical activity from the lifestyle behaviour covariates was associated with the baseline health score in the declin-
ers group. More specifically, non-physically active participants were associated with lower baseline scores. In the
other groups (i.e. moderate-stable, high-stable, low-stable) the average baseline health score was not significantly
associated with physical activity, smoking or alcohol consumption. Regarding the rate of change in the declin-
ers group and the high-stable group, non-drinking was associated with higher rates of deterioration. On the
contrary, in the low-stable group alcohol abstinence was associated with lower rates of deterioration. Lifestyle
covariates were not associated with the slope in the moderate-stable group, whereas the average rate of change in
the low-stable class was not significant.

Discussion
Based on a representative sample of older adults from Mexico, we generated a metric of health status in older age
incorporating multiple dimensions of functioning measures and identified different groups of ageing trajecto-
ries across 14 years of follow-up. The findings in our study are consistent with previous research indicating that
health outcome in older life is quite a heterogeneous process45–48. In our dataset, we identified four distinct latent
trajectories of health which we named as follows: “decliners”, “moderate-stable”, “high-stable” and “low-stable”.

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Class 1-Decliners Class 2-Moderate- Class 3-High-stable Class 4-Low-stable


(n = 3,161) stable (n = 1,824) (n = 8,247) (n = 756)
Estimate (SE)
Intercept Mean 68.27 (0.40)** 56.39 (1.31)** 75.83 (0.29)** 39.69 (1.32)**
Slope Mean −28.29 (1.31)** −7.71 (1.37)** −11.52 (0.31)** −6.46 (6.94)
Variance-Covariance Intercept 25.05 (2.38)**
Slope 20.44 (3.77)**
Intercept-Slope 17.05 (3.10)**
Logit Coefficients† Estimate (SE)
Physical Activity
0.33 (0.09)** −0.06 (0.28) Reference 2.17 (0.41)**
(Non-physically active vs active)
Ever smoking
−0.39 (0.09)** −0.28 (0.19) Reference −0.58 (0.20)**
(Never smokers vs current/former smokers)
Drinking of alcohol
0.19 (0.07)** 0.04 (0.17) Reference 0.48 (0.18)**
(Never and no drinkers vs drinkers)
Odds Ratio (95%CI)
Physical Activity
1.39 (1.17–1.66) 0.94 (0.54–1.63) Reference 8.78 (3.92–19.56)
(Non-physically active vs active)
Ever smoking
0.68 (0.57–0.81) 0.76 (0.52–1.10) Reference 0.56 (0.38–0.83)
(Never smokers vs current/former smokers)
Drinking of alcohol
1.21 (1.05–1.39) 1.04 (0.75–1.45) Reference 1.62 (1.14–2.30)
(Never and no drinkers vs drinkers)

Table 3.  Estimates and standard errors for the four-class growth mixture model of health. Notes. SE: standard
errors. **statistically significant in 0.05 level; *statistically significant in 0.10 level; †adjusted for sex, age and
education level.

Decliners are people who started with a high level of health in the baseline but exhibited the worst decline in the
follow-up waves and a high death probability. The moderate-stable class had those participants starting in a mod-
erate level and continue within a moderate level; this group could represent the usual agers. On the contrary, the
high-stable group includes individuals who started high and concluded with a high level of health after 14 years
of follow-up and the lowest death probability. This group could be characterised as the one exhibiting the ideal
ageing trajectory. Finally, the low-stable class, representing the unhealthy agers, encompasses those participants
who started low and finished low and exhibited the greatest probability of death in 2015.
Our findings regarding the number of distinct trajectories agree in general with research in high-income
countries, even though a unanimous consensus regarding the number of identified latent classes is lacking.
For instance, a study with data (n = 798; 9 years of follow-up) from the InCHIANTI cohort (Italy) and the
Longitudinal Aging Study Amsterdam (LASA) suggested three different trajectories in the functional decline
status of people 60–70 years old (no/little decline, intermediate decline, severe decline)46. Three distinct tra-
jectories of ageing well (stable-good ageing well; initially ageing well then deteriorating; stable-poor) were also
identified in a sample (n = 1,000; 16 years of follow-up) from the Melbourne Longitudinal Studies on Healthy
Ageing (MELSHA)45. On the contrary and in agreement with our findings, Hsu and Jones (2012) identified four
distinct trajectories (successful ageing; usual aging; health declining; and care demanding) in a study with older
Taiwanese49. Three to four distinct trajectories were also identified in another LASA study where the focus was
the cognitive and functional indicator of successful ageing, respectively50. Variety in the operational definitions of
health outcomes in older age, differences in the study designs (i.e. sample size, follow-up time) seem to consider-
ably impact the number of the identified trajectories.
In our analyses, participants with history of physical inactivity, smoking and alcohol abstinence were associ-
ated with an increased risk of accelerated decline in health and consistent poor health during the ageing process.
These findings are in accordance with other studies indicating the beneficial effect of healthy lifestyle behaviour
for a better ageing8,51,52. Physical activity was the strongest marker of the classes with non-physically active par-
ticipants being almost 9 times more likely to be in the low-stable group compare to the high-stable group. Other
studies using Mexican cohorts have also indicated that physical activity is associated with a decreased risk of
cognitive decline and disability53,54. Our study replicated the finding that smoking abstinence is beneficially asso-
ciated with better health outcomes in later life8,13. Regarding alcohol consumption, we found that it is a marker
of better ageing trajectories in accordance with other studies reporting a beneficial association of light alcohol
consumption with reduced risk of functional health decline55. However, these findings should be interpreted with
caution as there are contradictory findings regarding the beneficial effect of limited alcohol consumption56,57.
To the best of our knowledge, this is the first study that examined healthy ageing in a longitudinal framework
in a representative older cohort of Mexican people. The benefit of the conditional GMM approach is that it can
identify these latent classes which indicate a consistent low functioning or a steep deterioration. Hence, by this
way it can help researchers and policymakers to focus on those who are in risk and target them for future inter-
ventions. From a methodological point of view, the implementation of a one-step approach in the estimation
of the GMM, which allowed the simultaneous incorporation of covariates, provides a more precise estimation
of the covariates effects as class memberships are treated as latent variables and thus findings are less prone to
measurement error58.

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Among the strengths of our study is the use of a Bayesian multilevel IRT model. To better capture the under-
lying variable of health in old age, we employed a measurement model and then used this as an outcome in our
GMM analyses. This approach allowed us to have different sets of questions per wave by also taking into account
between and within (across the waves) participants information and simultaneously estimate all parameters26.
The biggest strength of this model is that the latent construct of health was estimated in a multilevel framework
allowing item parameters to vary across waves, whereas a common measurement of health was preserved;23 this
feature allowed for the comparison of health metric among waves. Our measurement approach also contributed
to the operationalisation of health in older age on a continuum, avoiding the often employed but unrealistic
threshold approach (i.e. dichotomising participants as healthy or non-healthy agers)59. Additionally, our study
is among the first ones that employed functional ability items to operationalise healthy ageing in accordance
with the WHO framework17. Similar methodologies have recently been adopted in studies employing data from
cohorts in the UK and the USA48,60.
Limitations of this study include the high attrition rate occurred during the 14 years of follow-up. In our mod-
els we assumed MAR mechanism, however as in all longitudinal studies of older people, there is a significant attri-
tion due to death creating a survival bias towards healthier people. In addition, our analyses focused on people 50
years old and over without considering early life exposures. Nevertheless, a review has indicated the considerable
impact of early life factors and events to health outcomes in older age61. Furthermore, since we only adjusted for
age, gender and education level, the impact of lifestyle behaviours on the trajectories may be contributed to other
unadjusted confounding factors. Additionally, as all information was self-reported measurement errors could not
be excluded. Another limitation of our study is the way lifestyle behaviour variables were measured. The questions
about physical activity and alcohol were too broad not allowing to assess the impact of different frequencies and
intensities on the ageing trajectories. In particular, we could not identify former-excessive drinkers and investi-
gate the impact of alcohol abuse in early life on healthy ageing.
Our study focused on distal lifestyle predictors early in mid-life to identify opportunities for health mainte-
nance as people growing older. However, we also know that reverse causality could also be an issue, especially
for physical activity (i.e. better health as people age could also affect physical activity levels). As a result, future
research should focus on time-varying measures of physical activity that could help us to investigate the direction
of these causal pathways. Furthermore, a more precise and objective measurement of physical activity and alcohol
consumption could contribute to specifically identify the quantities that mostly improve or deteriorate health in
older populations. In addition, even though, GMM is a sensitive approach able to identify latent subpopulations,
it is data-driven and hugely dependable on the variation and characteristics of the sample. Future research should
also focus on replicating these findings and advance the current knowledge in the field, even though comparabil-
ity among cohorts is challenging. Finally, including younger cohorts in the analyses will contribute to a life-course
perspective investigation and to examine whether similar trajectories are also observed62,63.
In conclusion, our findings show that older Mexicans age by following different trajectories of health and
that lifestyle behaviours play an important role in these developmental processes. Physical activity and smoking
abstinence are associated with better ageing trajectories, as well as the non-alcohol avoidance. In accordance
with previous research, our results highlight the need for health policies and prevention strategies in the area11.
Establishing non-pharmacological interventions that promote the adoption of a healthy lifestyle from early on
could benefit older people to increase the number of years spent in a good health. In addition, it will assist gov-
ernments and societies to more effectively deal with the public health burden. This is particularly important as
Mexico will face a dramatic ageing population growth in the following years.

Ethical approval.  The MHAS study protocol and instruments were approved by the Institutional Review
Board or Ethics Committee of the University of Texas Medical Branch, the Instituto Nacional de Estadística y
Geografía (INEGI) in Mexico, and the Instituto Nacional de Salud Pública (INSP) in Mexico19,20. All selected
subjects signed informed consent when the study started and were free to refuse participation in the study. All
surveys completed by INEGI follow standard procedures to ensure respondent confidentiality and privacy of
information in accordance to the ethical standards of INEGI and with the Helsinki ethical standards64.

Data Availability
The data analysed during the current study were obtained by the official website of the Mexican Health and Aging
Study. Codes for the statistical analyses are available from the corresponding author on reasonable request.

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Acknowledgements
This work was supported by the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies
(ATHLOS) project. The ATHLOS project has received funding from the European Union’s Horizon 2020
research and innovation program under grant agreement No 635316. The MHAS (Mexican Health and Aging
Study) is partly sponsored by the National Institutes of Health/National Institute on Aging (grant number NIH
R01AG018016) and the INEGI in Mexico. Data files and documentation are public use and available at www.
MHASweb.org. The study is a collaborative effort of the University of Texas Medical Branch (UTMB), the Instituto
Nacional de Estadística y Geografía (INEGI, Mexico), the University of Wisconsin, the Instituto Nacional de
Geriatría (Inger, Mexico), and the Instituto Nacional de Salud Pública (INSP, Mexico).

Author Contributions
C.D. planned the study, performed all statistical analyses and wrote the paper. A.K. supervised the data analyses,
provided insight in the statistical analyses and contributed to paper writing. Y.-T.W. contributed to data
interpretation and the writing of this paper. G.M.T. provided insight in the statistical analyses and comments on
the first draft of this manuscript. F.F.C., J.F. and D.P. provided insight in the data analyses and contributed to paper
writing. S.T. contributed to data interpretation and the writing of this paper. M.P. (Martin Prince) supervised the
data analyses and contributed to paper writing. M.P. (Matthew Prina) supervised the data analyses, contributed
to data interpretation and paper writing.

Additional Information
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-47238-w.
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