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RESEARCH ARTICLE
Factors associated with Alzheimer’s disease
prevalence and mortality in Brazil—An
ecological study
Murilo BastosID
1,2*, Michael Pereira da Silva3, Danyele da Silva4, Glauco Nonose Negrão5,
Graziele SchumanskiID
6, Weber Claudio Francisco Nunes da SilvaID
5, Juliana
Sartori Bonini1,5
1 Laboratório de Neurociência e Comportamento, Universidade Estadual do Centro-Oeste, Guarapuava,
PR, Brazil, 2 Cline Research Center, Curitiba, PR, Brazil, 3 Faculty of Medicine, Federal University of Rio
Grande, Rio Grande, RS, Brazil, 4 Departamento de Enfermagem, Universidade Estadual do Centro-Oeste,
Guarapuava, PR, Brazil, 5 Associação de Estudos, Pesquisa e Assistência as Pessoas com Doença de
Alzheimer, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil, 6 Profnit, Universidade
Estadual do Centro-Oeste, Guarapuava, PR, Brazil
* murilo_bastos@yahoo.com.br
Abstract
A few epidemiological studies are evaluating the prevalence and mortality rates of Alzhei-
mer’s disease, with no one using a nationwide sample of Brazilian elderlies. This study aims
to calculate the prevalence of Alzheimer’s disease and investigate possible associations
with sociodemographic and lifestyle factors and the presence of diseases non-communica-
ble, and the prevalence and mortality for all Brazilian state capitals. This is an ecological
design study made with secondary public data provided by the Ministry of Health. Preva-
lence rates were calculated based on the analysis of the dispensing of Alzheimer’s disease-
specific drugs. Correlation analyzes were performed between rates and factors, and a multi-
ple linear regression analysis was used to analyze possible associations between variables,
controlled for each other. AD prevalence was 313/100,000. Prevalence rates were positively
associated with primary health care coverage factors and negatively associated with ultra-
processed food consumption and physical activity levels. AD mortality was 98/100,000. Mor-
tality rates were positively associated with the proportion of obese elderly and elderly living
on up to half the minimum wage and were inversely associated with the proportion of elderly
with diabetes factors. We found positive and negative associations of sociodemographic,
behavioral and diabetes indicators with Alzheimer’s disease prevalence and mortality,
which provide data that can be investigated by studies with different designs.
Introduction
Aging causes a wide range of molecular and cellular damage which leads to a gradual decrease
in physical and mental capacity, an increased risk of disease, and, ultimately, death [1]. It is
estimated that by 2050, 21.4% of the world’s population will be over 60 years old [1]. The Bra-
zilian Institute of Geography and Statistics estimates that in 2060, 25.5% of Brazilians will be
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OPEN ACCESS
Citation: Bastos M, da Silva MP, da Silva D,
Negrão GN, Schumanski G, da Silva WCFN, et al.
(2023) Factors associated with Alzheimer’s disease
prevalence and mortality in Brazil—An ecological
study. PLoS ONE 18(8): e0283936. https://doi.org/
10.1371/journal.pone.0283936
Editor: Leonardo Costa Pereira, Euro American
University Center, BRAZIL
Received: June 9, 2022
Accepted: March 19, 2023
Published: August 21, 2023
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
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https://doi.org/10.1371/journal.pone.0283936
Copyright: © 2023 Bastos et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: The data used in this
study are public, made available by the country’s
Ministry of Health and by entities linked to research
and the government. (https://cidades.ibge.gov.br/
https://orcid.org/0000-0003-0358-8738
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https://cidades.ibge.gov.br/brasil/panorama
over 65 years of age, and life expectancy might increase approximately 3 years (75.7 years in
2016 to 78.6 in 2030) [2].
Dementia syndromes are neurodegenerative diseases characterized by irreversible destruc-
tion of neurons resulting in a progressive and disabling loss of specific functions of the nervous
system [3]. Alzheimer’s Disease (AD) is the primary and most prevalent dementia, accounting
for about 60 to 70% of cases [4]. AD develops insidiously, continuously and slowly, having
advanced age as its main risk factor [3]. AD is also related to other factors such as reduced
brain cognitive reserve, reduced brain size, low educational level, low occupational complexity,
low levels of physical activity throughout life [5, 6], and poor nutritional status [7].
However, even with the increase in the elderly population and, consequently, the possible
increase in people with AD in Brazil, few epidemiological studies evaluated the AD prevalence
and mortality rates using a nationwide sample of Brazilian elderlies. In fact, data regarding AD
prevalence are restricted to specific states or cities [8–12] limiting the better understanding of
how AD is prevalent and impact the mortality rates in elderly Brazilian. Furthermore, it also
limits the knowledge of possible factors associated with the disease, such as sociodemographic,
lifestyle, and the presence of other chronic diseases.
The Brazilian Unified Health System (UHS) offers specific drugs for AD treatment free of
charge. Thus, AD prevalence might be estimated using data of the number of elderlies who
took these drugs from UHS. Therefore, this study aims to verify the AD’s prevalence and mor-
tality rates in all Brazilian state capitals. We also aimed to verify the association of sociodemo-
graphic, lifestyle, and other non-communicable diseases (NCDs) with AD prevalence and
mortality.
Methods
Design and estimates of prevalence and mortality
It is an ecological epidemiological study based on secondary data from 2019 provided by the
Brazilian Ministry of Health and the Health Indicators and Monitoring System for Elderly Pol-
icies (SISAP IDOSO) of the Oswaldo Cruz Foundation [13].
The Brazilian Unified Health System (UHS) offers specific drugs for AD treatment free of
charge through the diagnosis of probable AD according to the Clinical Protocol and Therapeu-
tic Guidelines [14]. This document establishes the criteria for the diagnosis and treatment and
is essential for the dispensing of medication. We calculated the AD prevalence using the num-
ber of elderlies who took specific drugs to treat AD from the Brazilian UHS and the total
elderly population of each state capital analyzed. The prevalence was expressed in cases for
each 100,000people (total number of patients/total population X 100,000 people). The data
was obtained from the SISAP IDOSO database [13]. The AD’s mortality rate, expressed in
deaths for each 100,000, was obtained from the Mortality Information System, accessed
through the Ministry of Health database [15] (https://datasus.saude.gov.br/mortalidade-desde-
1996-pela-cid-10), filtering mortality by AD (ICD G30) for each state capital for people aged
over 60 years.
Sociodemographic factors
The Human Development Index by cities (HDIm), Gini Index, per capita income, were
obtained from the Brazilian Institute of Geography and Statistics [16] (IBGE) and corre-
sponded to the most current data available since the last census was carried out in 2010.
The educational level was obtained from the VIGITEL Brazil survey in 2019 [17]. In addi-
tion, data on the percentage of elderly living on half (1/2) minimum wage and percentage of
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brasil/panorama) (https://www.saudeidoso.icict.
fiocruz.br/novo2/td_munic_5.php) (https://
datasus.saude.gov.br/mortalidade-desde-1996-
pela-cid-10) (http://svs.aids.gov.br/download/
Vigitel/).
Funding: The authors received no specific funding
for this work.
Competing interests: NO authors have competing
interests.
https://datasus.saude.gov.br/mortalidade-desde-1996-pela-cid-10
https://datasus.saude.gov.br/mortalidade-desde-1996-pela-cid-10
https://doi.org/10.1371/journal.pone.0283936
https://cidades.ibge.gov.br/brasil/panorama
https://www.saudeidoso.icict.fiocruz.br/novo2/td_munic_5.php
https://www.saudeidoso.icict.fiocruz.br/novo2/td_munic_5.php
https://datasus.saude.gov.br/mortalidade-desde-1996-pela-cid-10
https://datasus.saude.gov.br/mortalidade-desde-1996-pela-cid-10
https://datasus.saude.gov.br/mortalidade-desde-1996-pela-cid-10
http://svs.aids.gov.br/download/Vigitel/
http://svs.aids.gov.br/download/Vigitel/
elderly living on a quarter (1/4) of the minimum wage were taken from SISAP IDOSO [13]
and have 2010 as the year of reference.
Regarding the data on access to food, the Brazilian Scale of Food Insecurity was chosen,
applied in the 2017–2018 Family Budget Survey, and made available by the IBGE portal [18],
which ranks based on the score of nine questions about access to food and classifies the house-
hold in food security (FS) and food insecurity (FI), the latter still stratified into mild, moderate,
and severe. However, in this study, we only used the FI data in the associations.
The data of primary health care coverage (PHC) were taken from the e-manager portal of
the Ministry of Health [19] (https://egestorab.saude.gov.br/index.xhtml), reference year was
2019, with PHC coverage defined as estimated population coverage in Primary Care, given by
the percentage of the population covered by teams from the Family Health Strategy and by
teams of equivalent traditional Primary Care, parameterized concerning the population
estimate.
Lifestyle factors
The Physical Activity Level (PAL), considered as the percentage of elderly who practiced at
least 150 minutes of moderate to vigorous physical activity (PA) per week; Ultra-processed
foods consumption, considered as a percentage of the elderly population that consumes five or
more servings of ultra-processed foods per day; Consumption of protective foods, considered
as a percentage of the elderly population that consumes five or more minimally or unprocessed
foods per day; Overweight, considered as a percentage of the elderly population with a body
mass index (BMI) between 25 and 29.9 kg/m2; Obesity; considered as BMI� 30kg/m2, were
obtained from the VIGITEL 2019 survey [17].
Statistical analysis
The Shapiro-Wilk test verified data normality. Pearson’s correlation analyzed the association
between mortality rates and obesity, physical activity level, hypertension, the proportion of
elderly living on half the minimum wage, consumption of protective foods, food insecurity,
HDIm, and Gini index. Spearman’s correlation test analyzed the association between the vari-
ables prevalence and women mortality rates, and the variables ultra-processed foods consump-
tion, high educational level, and PHC.
Multiple linear regression analyzed the independent association of sociodemographic, life-
style factors, and the presence of NCDs with AD prevalence and mortality rates. The variables
of each model were included hierarchically and we dropped variables with p>0.20 using the
backward procedure. The statistical significance level was set at p(p = 0,01) 0,60* (p0.15 that did not enter the final regression model. B: linear
regression coefficient; 95%CI: Confidence Interval; p: level of statistical significance; High educational level:
education range between 15 and 20 years of study; HDIm; Human Development Index by cities; PHC coverage:
primary health care coverage; Food Insecurity: Proportion of population with food insecurity according to the
Brazilian Food Insecurity Scale. PAL: Physical activity level considering 3 domains.
https://doi.org/10.1371/journal.pone.0283936.t002
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of dementia and AD on the mortality rates might be underestimated [32] since AD can make
the elderly more vulnerable to other diseases that lead to death [33], in addition to the difficulty
in determining the number of deaths caused by AD due to the way of recording the cause of
death [34]. Therefore, even if AD does not occupy a high place in the ranking of causes of
death in Brazilian elderlies, AD may be associated with other comorbidities that lead to elderly
deaths, reinforcing the need of further investigation.
This study found that capitals with higher PHC coverage had higher AD prevalence. PHC
is characterized by a set of individual and collective health actions, covering aspects of health
promotion, disease prevention, diagnosis, treatment, rehabilitation, harm reduction, and
health maintenance [35]. Elderlies with the subjective cognitive decline with a higher number
of medical appointments had more frequent memory complaints than those with a lower
number of appointments [36]. In Brazil, the elderly with AD visits a clinician more frequently
compared to the elderly without AD, on the other hand, these individuals had fewer appoint-
ments with specialists [37]. Brazilian state capitals with higher PHC coverage might be more
successful in screening AD cases because the healthcare system is more accessible to the com-
munity, especially those with lowest economic level.
PAL prevalence was inversely related to AD’s prevalence. For elderlies, the PA recommen-
dation for substantial health benefits, including mental health, is 150–300 minutes of moder-
ate-intensity, or 75–150 minutes of vigorous intensity, per week [38]. Physical inactivity
presents a 12.7% population-attributable risk for AD worldwide and 21% for the US popula-
tion [39]. In Brazil, the proportion of physically inactive elderly with AD was also higher com-
pared to the elderly without AD [37]. Furthermore, a 20% reduction in the risk of developing
dementia was attributed to engaging in any physical activity [36]. Therefore, our hypothesis
was confirmed, that AD maybe was also influenced by the adequate PAL, engaging in PAprac-
tice can slow down cognitive decline in elderly people with high concentrations of tau protein
in the brain compared to elderly people with low PAL [40].
A higher proportion of elderly who consume five or more servings of ultra-processed foods
were inversely associated with the AD’s prevalence. The western standard of diet, composed of
a good amount of processed foods with high levels of saturated fat and sugar, results in consid-
erable adverse health effects [41], and these effects are not different to dementia and AD. Diets
with high amounts of saturated fat and sugar worsened Aβ-42 concentrations in cerebrospinal
fluid (FCS), which is an AD marker, compared to low amounts of fat and sugar diets [42]. Fur-
thermore, dietary patterns such as the Mediterranean Diet, characterized by high consumption
of fruits, vegetables, vegetables and cereals, olive oil, and moderate consumption of alcohol
and red meat, are associated with lower rates of cognitive decline and significant reductions in
AD rates [43]. However, we found an inverse association between consumption of ultra-pro-
cessed foods and the prevalence of AD. As both variables refer to the same year, maybe the
time of exposure to the risk factor consumption of ultra-processed food consumption has not
yet been sufficient to cause an impact on the Alzheimer’s disease prevalence. Thus, further
investigation should monitor the impact of ultra-processed food on the Alzheimer’s disease
using a longitudinal design.
Our study showed that state capitals with higher diabetes prevalence had higher AD mortal-
ity rates. Type 2 Diabetes Mellitus (T2D) increases the risk of several types of dementia, includ-
ing AD, through the formation of vascular lesions and ischemia, changing metabolic processes
in the central nervous system, maintaining a chronic inflammatory process [44]. Furthermore,
due to numerous similarities between diabetes and AD, some authors have called AD "Type 3
Diabetes" [45]. However, there seem to be no significant differences in in-hospital mortality
between AD patients who had or did not have T2D, with only the risk ratio for the sum of
comorbidities being significant [46]. Therefore, as the present study found that capitals with a
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https://doi.org/10.1371/journal.pone.0283936
higher prevalence of T2D have higher AD’s mortality and judging by the fewer studies specifi-
cally evaluating this association, further investigation should be carried out to better under-
stand this relationship. However, regarding the difference between the result found in this
study and the literature, one aspect of the potential for metabolic overlap of the two diseases,
which makes any conclusions more difficult [47].
Finally, our study found a significant and negative association between the obesity preva-
lence and the AD’s mortality. Although the literature presents data related to a more accentu-
ated cognitive impairment in obese individuals (BMI�30 kg/m2) [48, 49], the relationship
with AD’s mortality presents results conflicting. For example, a greater body mass index can
be protective against AD’s death and is inversely related to medial temporal atrophy [7]. On
the other hand, lower BMI is associated with faster cognitive decline [50, 51]. These findings
may seem somewhat contradictory, especially about a desirable BMI. Lower body mass may be
associated with lower energy consumption and, consequently, nutrient intake below the physi-
ological needs. However, there is also the assumption that a lower body mass is associated with
a higher resting metabolic rate in patients with AD [52]. Therefore, this study indicated that a
higher BMI can be protective against AD mortality which might be explained by a higher
energy reserve. However further investigation on the individual level should explore how BMI
mediates AD mortality.
The present study has limitations. The adopted ecological design uses as a sampling unit a
group of individuals and non-individuals, and this can interfere with the results. However, the
data analyzed here are representative of the population of the capitals and present essential
data for future studies using different research designs. Another limitation is the method of
estimating AD’s prevalence that used data on free dispensing of specific drugs for AD treat-
ment by the public health system, which would limit the sample to only users of this system.
However, we believe that this limitation does not reduce the importance of our findings since
the system’s user population is quite large and representative.
In conclusion, this study found a low prevalence of AD among the Brazilian elderly (300
cases per 100,000 elderly). Furthermore, we found an AD’s mortality rate of 36 deaths per
100,00 elderlies. AD’s prevalence was positively associated with PHC coverage and negatively
associated with ultra-processed foods consumption and PAL. AD’s mortality rate was inversely
associated with the proportion of obese elderly and elderly living on up to half the minimum
wage and positively associated with diabetes prevalence.
Acknowledgments
I am grateful for the collaboration of MPS, for data analysis and writing, GNN, for database
suggestions, JSB, for the thorough review, and other authors for writing and final review.
Author Contributions
Conceptualization: Murilo Bastos, Michael Pereira da Silva, Glauco Nonose Negrão, Graziele
Schumanski, Weber Claudio Francisco Nunes da Silva, Juliana Sartori Bonini.
Data curation: Murilo Bastos, Michael Pereira da Silva.
Investigation: Murilo Bastos.
Methodology: Murilo Bastos, Michael Pereira da Silva, Danyele da Silva, Glauco Nonose
Negrão, Juliana Sartori Bonini.
Supervision: Weber Claudio Francisco Nunes da Silva, Juliana Sartori Bonini.
Validation: Juliana Sartori Bonini.
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https://doi.org/10.1371/journal.pone.0283936
Writing – original draft: Murilo Bastos, Michael Pereira da Silva, Danyele da Silva.
Writing – review & editing: Danyele da Silva, Glauco Nonose Negrão, Graziele Schumanski,
Weber Claudio Francisco Nunes da Silva, Juliana Sartori Bonini.
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