Original Paper Received: August 31, 2014 Accepted: January 22, 2015 Published online: March 7, 2015
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
Association between Stressful Life Events and Cognitive Disorders in Central Africa: Results from the EPIDEMCA Program Sophie Pilleron a, b Maëlenn Guerchet a–c Bébène Ndamba-Bandzouzi a, b, d Pascal Mbelesso a, b, e Jean-Francois Dartigues f Pierre-Marie Preux a, b, g Jean-Pierre Clément a, b, h for the EPIDEMCA Group
a INSERM, U1094, Tropical Neuroepidemiology, b University Limoges, UMR_S 1094, Tropical Neuroepidemiology, Institute of Neuroepidemiology and Tropical Neurology, CNRS FR 3503 GEIST, Limoges, France; c King’s College London, Centre for Global Mental Health, Institute of Psychiatry, Health Service and Population Research Department, London, UK; d Department of Neurology, Brazzaville University Hospital, Brazzaville, Republic of Congo; e Department of Neurology, Amitié Hospital, Bangui, Central African Republic; f INSERM U897, Bordeaux University, Bordeaux, g CHU Limoges, Centre of Epidemiology, Biostatistic, and Research Methodology, CEBIMER, h Hospital and University Federation of Adult and Geriatric Psychiatry, Limoges, France
Key Words Stressful life events · Dementia · Mild cognitive impairment · Central Africa
Abstract Background: Stressful life events (SLEs) are considered potential risk factors for cognitive disorders. Our objective was to investigate the association between SLEs and cognitive disorders among the elderly people in Central Africa. Method: A population-based study was conducted in the Central African Republic (CAR) and the Republic of Congo (ROC). Participants aged ≥65 were interviewed using the Community Screening Interview for Dementia. Those who performed poorly were clinically assessed by neurologists. DSM-IV and Petersen criteria were required for a diagnosis of dementia or mild cognitive impairment (MCI), respectively. SLEs were assessed through 18 questions about events that occurred during childhood, adulthood and late-life. Sociodemographic, vascular and psychological factors were
© 2015 S. Karger AG, Basel 0251–5350/15/0442–0099$39.50/0 E-Mail [email protected] www.karger.com/ned
also documented. Multivariate multinomial logistic regression models were used to estimate the associations. Results: MCI was positively associated with: the total number of SLEs (OR = 1.1, 95% CI: 1.0–1.2), the number of SLEs from the age of 65 (OR = 1.2, 95% CI: 1.0–1.3), the number of SLEs before the age of 16 among non-depressive participants (OR = 1.6, 95% CI: 1.2–2.2) and with a serious illness in a child experienced when the participant was aged 65 or more (OR = 2.8, 95% CI: 1.6–4.6). No association with dementia was observed. Conclusion: SLEs were positively associated with MCI but not dementia. More comprehensive studies are needed to further investigate this relationship. © 2015 S. Karger AG, Basel
EPIDEMCA Group: Maëlenn Guerchet, Bébène Ndamba-Bandzouzi, Pascal Mbelesso, Sophie Pilleron, Iléana Désormais, Philippe Lacroix, Victor Aboyans, Jean-Claude Desport, Pierre Jésus, Achille E. Tchalla, Benoît Marin, Jean-Pierre Clément, Jean-Charles Lambert, Jean-François Dartigues and Pierre-Marie Preux.
Prof. Jean-Pierre Clément INSERM, UMR 1094, Tropical Neuroepidemiology Faculté of Médecine, 2, Rue du Docteur Marcland FR–87025 Limoges (France) E-Mail jean-pierre.clement @ numericable.com
Downloaded by: Kungliga Tekniska Hogskolan 198.143.54.65 - 1/26/2016 10:09:57 PM
By 2050, Africa is expected to experience a phenomenal increase in the number of cases of dementia (+344%) than anywhere else in the world [1]. However, epidemiological studies are still scarce in this continent, even if interest in dementia is growing as shown by the number of studies published in the past 10 years. In a biopsychosocial approach to dementia, western research focused on stressful life events (SLEs) as potential risk factors for cognitive disorders in old age. The first longitudinal study investigating this relationship was reported by Persson and Skoog [2]. In a cohort of people aged 70 followed up after 5 and 9 years, they showed that parental death before the age of 16, arduous manual work during adulthood, spouse death and a serious illness in a child after the age of 65 were predictors of dementia and considered to be psychosocial risk factors. Furthermore, there was a dose-effect relationship between the number of SLEs and the risk of dementia. This preliminary study opened the way to others. Norton et al. confirmed that parental death during childhood was a risk factor for dementia and Alzheimer’s disease [3, 4]. Ravona-Springer et al. reported that the crisis following parental death would be a risk factor for dementia, particularly when the parental death occurred early in childhood [5]. In a 35-year longitudinal study, Johansson et al. showed that having experienced chronic stress during adulthood predicted the risk of dementia [6] as well as increasing the risk of cerebral atrophy and white matter lesions in old age [7], and all these changes related to dementia. Peavy et al. showed that recent stressful life events predicted faster cognitive decline among subjects with mild cognitive impairment (MCI) [8] and a dementia diagnosis [9]. However, life events did not predict MCI diagnosis, suggesting a different effect of SLEs depending on the level of hippocampal injury [9]. More recently, a longitudinal study with a follow up of 10.8 years contradicted all these previous results, finding no association between aggregated or individual SLEs – including no events in childhood – and dementia [10]. All these aforementioned studies were conducted in western industrialized countries. In the African continent, some studies investigated SLEs as potential factors associated with cognitive impairment or dementia. In Benin, no association was found with cognitive impairment [11]. In contrast, a multicentre study carried out in two capitals of Central Africa, Bangui in the Central African Republic (CAR) and Brazzaville in the Republic of Congo (ROC), found that parental death before the age of 16 and recent house moving were independently associated with de100
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
mentia [12]. However, this study did not investigate the relationship with either MCI or the number of life events. In the present study, we wished to elucidate the relationship between SLEs and cognitive disorders in the elderly, knowledge of which is essentially limited to westernized countries, in a different culture. We also hoped to confirm previous results in CAR and ROC. We tested several hypotheses. First, that a higher number of events is associated with an increased probability of cognitive disorders. Then, that one or more SLEs during childhood, especially parental death, increase the deleterious effect of later SLEs on the likelihood of cognitive disorders. Finally, that some individual SLEs, especially during childhood or over the age of 65, two periods of greater cerebral vulnerability to stress, are associated with an increased probability of cognitive disorders while others are not. This study is part of the Epidemiology of Dementia in Central Africa (EPIDEMCA) program whose main objectives were to estimate the prevalence of dementia and cognitive disorders in rural and urban areas of ROC and CAR and to evaluate associated factors.
Method Study Population Our study population consisted of participants in the EPIDEMCA program – a multicentre community-based, crosssectional study conducted in CAR and ROC between November 2011 and December 2012. The detailed methodology is published in an open access publication [13]. In brief, subjects aged 65 and above who had lived in the study area for at least six months were included. The study areas included the capitals of CAR (Bangui) and ROC (Brazzaville), and two rural regions (Nola in CAR and Gamboma in ROC). The sample size calculated was 500 in each site. In urban areas, the selection was carried out using random sampling that was proportional to the main city subdivision size. In rural areas, exhaustive sampling using a door-to-door approach was preferred due to logistic and financial constraints. Approvals were obtained from the Ministry of Public Health in CAR, the CERSSA (Comité d’Éthique de la Recherche en Sciences de Santé) in ROC, and the CPPSOOM-4 (Comité de Protection des Personnes du Sud-Ouest et d’Outre-Mer 4) in France. All participants and/or their families gave informed consent before being included in the study. Assessment of Cognitive Disorders Cognitive disorders were assessed in two phases. During the first phase, cognitive testing was performed using the Community Screening Interview for Dementia (CSI-D) [14] adapted, backtranslated and pretested in the local languages (Sango in CAR, Lari, Lingala, and Kituba in ROC). The CSI-D is a transcultural screening instrument developed specifically for use in low- and middleincome populations with low education levels. It has two sections: a cognitive section and an informant section where a close family
Pilleron et al.
Downloaded by: Kungliga Tekniska Hogskolan 198.143.54.65 - 1/26/2016 10:09:57 PM
Introduction
Assessment of Stressful Life Events During the first phase, the subjects, or their informants in cases of obvious cognitive disorder, were asked about stressful life events using the questionnaire used by Persson and Skoog [2], which had already been applied in previous studies in Central Africa [12] and Benin [11]. Life events were originally selected because they would give rise to stress reactions in most people and are independent of the actions of the individual [2]. The questionnaire captures five life events before the age of 16 (death of a parent, divorce of parents, growing up with one parent, different guardians, and extreme poverty), five life events between 16 and 65 years of age (death of spouse, death of a child, serious illness in a child, arduous manual work, and work at night) and eight life events at 65 and above (death of spouse, new physical illness in spouse, new mental illness in spouse, death of a child, serious illness in a child, marked reduction in contacts due to death of siblings or friends, reduction in social contacts due to enforced change in residence, and deterioration in financial status).
SLEs were considered in three ways: total number of lifetime events as a continuous variable; number of events by life period (childhood, adulthood and old age) as continuous variables, and each individual event separately as dichotomous variables. All covariates were used as categorical variables, except for age, which was used as a continuous variable since a linearity hypothesis could not be rejected. Means with their standard deviation were used as summary statistics for age and the number of SLEs. Percentages were calculated for all categorical variables. Bivariate analyses were carried out between our dependent variable and our independent variables, on the one hand, and between each of these variables and all potential covariates on the other, using the χ2 test, the Student ttest or ANOVA when appropriate. Multinomial logistic regression models were used to estimate the unadjusted and adjusted associations between cognitive disorders and SLEs. The Wald χ2 test was used in the final multivariate model to test interactions between SLEs and country, sex and depression, and also the effect of SLEs that occurred during childhood on the one hand and parental death on the other on the association between SLEs that occurred later and cognitive disorders. The level of significance was fixed at 0.05 for all analyses. Statistical analyses were carried-out using Stata version 10.1 for Windows (StataCorp, College Station, Tex., USA).
Results
Data Management and Analysis Cognitive disorders used as a categorical variable were our dependent variable consisting of three categories: cognitively normal, MCI, and dementia. Regarding our independent variables,
Characteristics of Study Participants During the first phase in the general population, 2,113 people aged 65 and above were approached; 111 declined to participate in the survey. Of the remaining 2,002 participants, 775 were invited to clinical interview and 555 actually came. At the end of the second phase, 118 had MCI, 135 had dementia (including 103 AD and 15 with vascular dementia) and 1,519 had normal cognition. We did not have neurological data for 229 subjects, who were therefore excluded from our analysis. One participant was excluded because of missing age, leaving 1,772 participants for analysis. The detailed flow chart is presented in figure 1. Subjects excluded were younger (73.1 (SD 6.7) vs. 74.8 (SD 6.7), p < 0.001), mainly females (79.5 vs. 59.1%, p < 0.001), single or widowed (19.2 vs. 38.9%, p < 0.001), less educated (12.7 vs. 33.6%, p < 0.001), and more depressed (49.3 vs. 36.6%, p < 0.001) (data not shown). Table 1 presents the general characteristics of the 1,772 EPIDEMCA participants included according to their cognitive status. People with cognitive disorders were significantly older, predominantly female (p < 0.001), single or widowed (p < 0.001), more likely to have no formal education (p < 0.001), to be alcohol abstainers (p < 0.001), to have a decreased BMI (p < 0.001), depressive symptoms (p < 0.001), and a dependent personality disorder (p < 0.001).
Stressful Life Events and Cognitive Disorders in Central Africa
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
Other Data Collected All covariates were collected during the first phase. Sociodemographic data included age, sex, marital status, formal education, country (CAR; ROC) and area (urban; rural). Age was ascertained from official documents using historical events [21] or from an informant if previous methods were unsuccessful. Body mass index (BMI) was used as a categorical variable consisting of three modalities:
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
Association between Stressful Life Events and Cognitive Disorders in Central Africa: Results from the EPIDEMCA Program Sophie Pilleron a, b Maëlenn Guerchet a–c Bébène Ndamba-Bandzouzi a, b, d Pascal Mbelesso a, b, e Jean-Francois Dartigues f Pierre-Marie Preux a, b, g Jean-Pierre Clément a, b, h for the EPIDEMCA Group
a INSERM, U1094, Tropical Neuroepidemiology, b University Limoges, UMR_S 1094, Tropical Neuroepidemiology, Institute of Neuroepidemiology and Tropical Neurology, CNRS FR 3503 GEIST, Limoges, France; c King’s College London, Centre for Global Mental Health, Institute of Psychiatry, Health Service and Population Research Department, London, UK; d Department of Neurology, Brazzaville University Hospital, Brazzaville, Republic of Congo; e Department of Neurology, Amitié Hospital, Bangui, Central African Republic; f INSERM U897, Bordeaux University, Bordeaux, g CHU Limoges, Centre of Epidemiology, Biostatistic, and Research Methodology, CEBIMER, h Hospital and University Federation of Adult and Geriatric Psychiatry, Limoges, France
Key Words Stressful life events · Dementia · Mild cognitive impairment · Central Africa
Abstract Background: Stressful life events (SLEs) are considered potential risk factors for cognitive disorders. Our objective was to investigate the association between SLEs and cognitive disorders among the elderly people in Central Africa. Method: A population-based study was conducted in the Central African Republic (CAR) and the Republic of Congo (ROC). Participants aged ≥65 were interviewed using the Community Screening Interview for Dementia. Those who performed poorly were clinically assessed by neurologists. DSM-IV and Petersen criteria were required for a diagnosis of dementia or mild cognitive impairment (MCI), respectively. SLEs were assessed through 18 questions about events that occurred during childhood, adulthood and late-life. Sociodemographic, vascular and psychological factors were
© 2015 S. Karger AG, Basel 0251–5350/15/0442–0099$39.50/0 E-Mail [email protected] www.karger.com/ned
also documented. Multivariate multinomial logistic regression models were used to estimate the associations. Results: MCI was positively associated with: the total number of SLEs (OR = 1.1, 95% CI: 1.0–1.2), the number of SLEs from the age of 65 (OR = 1.2, 95% CI: 1.0–1.3), the number of SLEs before the age of 16 among non-depressive participants (OR = 1.6, 95% CI: 1.2–2.2) and with a serious illness in a child experienced when the participant was aged 65 or more (OR = 2.8, 95% CI: 1.6–4.6). No association with dementia was observed. Conclusion: SLEs were positively associated with MCI but not dementia. More comprehensive studies are needed to further investigate this relationship. © 2015 S. Karger AG, Basel
EPIDEMCA Group: Maëlenn Guerchet, Bébène Ndamba-Bandzouzi, Pascal Mbelesso, Sophie Pilleron, Iléana Désormais, Philippe Lacroix, Victor Aboyans, Jean-Claude Desport, Pierre Jésus, Achille E. Tchalla, Benoît Marin, Jean-Pierre Clément, Jean-Charles Lambert, Jean-François Dartigues and Pierre-Marie Preux.
Prof. Jean-Pierre Clément INSERM, UMR 1094, Tropical Neuroepidemiology Faculté of Médecine, 2, Rue du Docteur Marcland FR–87025 Limoges (France) E-Mail jean-pierre.clement @ numericable.com
Downloaded by: Kungliga Tekniska Hogskolan 198.143.54.65 - 1/26/2016 10:09:57 PM
By 2050, Africa is expected to experience a phenomenal increase in the number of cases of dementia (+344%) than anywhere else in the world [1]. However, epidemiological studies are still scarce in this continent, even if interest in dementia is growing as shown by the number of studies published in the past 10 years. In a biopsychosocial approach to dementia, western research focused on stressful life events (SLEs) as potential risk factors for cognitive disorders in old age. The first longitudinal study investigating this relationship was reported by Persson and Skoog [2]. In a cohort of people aged 70 followed up after 5 and 9 years, they showed that parental death before the age of 16, arduous manual work during adulthood, spouse death and a serious illness in a child after the age of 65 were predictors of dementia and considered to be psychosocial risk factors. Furthermore, there was a dose-effect relationship between the number of SLEs and the risk of dementia. This preliminary study opened the way to others. Norton et al. confirmed that parental death during childhood was a risk factor for dementia and Alzheimer’s disease [3, 4]. Ravona-Springer et al. reported that the crisis following parental death would be a risk factor for dementia, particularly when the parental death occurred early in childhood [5]. In a 35-year longitudinal study, Johansson et al. showed that having experienced chronic stress during adulthood predicted the risk of dementia [6] as well as increasing the risk of cerebral atrophy and white matter lesions in old age [7], and all these changes related to dementia. Peavy et al. showed that recent stressful life events predicted faster cognitive decline among subjects with mild cognitive impairment (MCI) [8] and a dementia diagnosis [9]. However, life events did not predict MCI diagnosis, suggesting a different effect of SLEs depending on the level of hippocampal injury [9]. More recently, a longitudinal study with a follow up of 10.8 years contradicted all these previous results, finding no association between aggregated or individual SLEs – including no events in childhood – and dementia [10]. All these aforementioned studies were conducted in western industrialized countries. In the African continent, some studies investigated SLEs as potential factors associated with cognitive impairment or dementia. In Benin, no association was found with cognitive impairment [11]. In contrast, a multicentre study carried out in two capitals of Central Africa, Bangui in the Central African Republic (CAR) and Brazzaville in the Republic of Congo (ROC), found that parental death before the age of 16 and recent house moving were independently associated with de100
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
mentia [12]. However, this study did not investigate the relationship with either MCI or the number of life events. In the present study, we wished to elucidate the relationship between SLEs and cognitive disorders in the elderly, knowledge of which is essentially limited to westernized countries, in a different culture. We also hoped to confirm previous results in CAR and ROC. We tested several hypotheses. First, that a higher number of events is associated with an increased probability of cognitive disorders. Then, that one or more SLEs during childhood, especially parental death, increase the deleterious effect of later SLEs on the likelihood of cognitive disorders. Finally, that some individual SLEs, especially during childhood or over the age of 65, two periods of greater cerebral vulnerability to stress, are associated with an increased probability of cognitive disorders while others are not. This study is part of the Epidemiology of Dementia in Central Africa (EPIDEMCA) program whose main objectives were to estimate the prevalence of dementia and cognitive disorders in rural and urban areas of ROC and CAR and to evaluate associated factors.
Method Study Population Our study population consisted of participants in the EPIDEMCA program – a multicentre community-based, crosssectional study conducted in CAR and ROC between November 2011 and December 2012. The detailed methodology is published in an open access publication [13]. In brief, subjects aged 65 and above who had lived in the study area for at least six months were included. The study areas included the capitals of CAR (Bangui) and ROC (Brazzaville), and two rural regions (Nola in CAR and Gamboma in ROC). The sample size calculated was 500 in each site. In urban areas, the selection was carried out using random sampling that was proportional to the main city subdivision size. In rural areas, exhaustive sampling using a door-to-door approach was preferred due to logistic and financial constraints. Approvals were obtained from the Ministry of Public Health in CAR, the CERSSA (Comité d’Éthique de la Recherche en Sciences de Santé) in ROC, and the CPPSOOM-4 (Comité de Protection des Personnes du Sud-Ouest et d’Outre-Mer 4) in France. All participants and/or their families gave informed consent before being included in the study. Assessment of Cognitive Disorders Cognitive disorders were assessed in two phases. During the first phase, cognitive testing was performed using the Community Screening Interview for Dementia (CSI-D) [14] adapted, backtranslated and pretested in the local languages (Sango in CAR, Lari, Lingala, and Kituba in ROC). The CSI-D is a transcultural screening instrument developed specifically for use in low- and middleincome populations with low education levels. It has two sections: a cognitive section and an informant section where a close family
Pilleron et al.
Downloaded by: Kungliga Tekniska Hogskolan 198.143.54.65 - 1/26/2016 10:09:57 PM
Introduction
Assessment of Stressful Life Events During the first phase, the subjects, or their informants in cases of obvious cognitive disorder, were asked about stressful life events using the questionnaire used by Persson and Skoog [2], which had already been applied in previous studies in Central Africa [12] and Benin [11]. Life events were originally selected because they would give rise to stress reactions in most people and are independent of the actions of the individual [2]. The questionnaire captures five life events before the age of 16 (death of a parent, divorce of parents, growing up with one parent, different guardians, and extreme poverty), five life events between 16 and 65 years of age (death of spouse, death of a child, serious illness in a child, arduous manual work, and work at night) and eight life events at 65 and above (death of spouse, new physical illness in spouse, new mental illness in spouse, death of a child, serious illness in a child, marked reduction in contacts due to death of siblings or friends, reduction in social contacts due to enforced change in residence, and deterioration in financial status).
SLEs were considered in three ways: total number of lifetime events as a continuous variable; number of events by life period (childhood, adulthood and old age) as continuous variables, and each individual event separately as dichotomous variables. All covariates were used as categorical variables, except for age, which was used as a continuous variable since a linearity hypothesis could not be rejected. Means with their standard deviation were used as summary statistics for age and the number of SLEs. Percentages were calculated for all categorical variables. Bivariate analyses were carried out between our dependent variable and our independent variables, on the one hand, and between each of these variables and all potential covariates on the other, using the χ2 test, the Student ttest or ANOVA when appropriate. Multinomial logistic regression models were used to estimate the unadjusted and adjusted associations between cognitive disorders and SLEs. The Wald χ2 test was used in the final multivariate model to test interactions between SLEs and country, sex and depression, and also the effect of SLEs that occurred during childhood on the one hand and parental death on the other on the association between SLEs that occurred later and cognitive disorders. The level of significance was fixed at 0.05 for all analyses. Statistical analyses were carried-out using Stata version 10.1 for Windows (StataCorp, College Station, Tex., USA).
Results
Data Management and Analysis Cognitive disorders used as a categorical variable were our dependent variable consisting of three categories: cognitively normal, MCI, and dementia. Regarding our independent variables,
Characteristics of Study Participants During the first phase in the general population, 2,113 people aged 65 and above were approached; 111 declined to participate in the survey. Of the remaining 2,002 participants, 775 were invited to clinical interview and 555 actually came. At the end of the second phase, 118 had MCI, 135 had dementia (including 103 AD and 15 with vascular dementia) and 1,519 had normal cognition. We did not have neurological data for 229 subjects, who were therefore excluded from our analysis. One participant was excluded because of missing age, leaving 1,772 participants for analysis. The detailed flow chart is presented in figure 1. Subjects excluded were younger (73.1 (SD 6.7) vs. 74.8 (SD 6.7), p < 0.001), mainly females (79.5 vs. 59.1%, p < 0.001), single or widowed (19.2 vs. 38.9%, p < 0.001), less educated (12.7 vs. 33.6%, p < 0.001), and more depressed (49.3 vs. 36.6%, p < 0.001) (data not shown). Table 1 presents the general characteristics of the 1,772 EPIDEMCA participants included according to their cognitive status. People with cognitive disorders were significantly older, predominantly female (p < 0.001), single or widowed (p < 0.001), more likely to have no formal education (p < 0.001), to be alcohol abstainers (p < 0.001), to have a decreased BMI (p < 0.001), depressive symptoms (p < 0.001), and a dependent personality disorder (p < 0.001).
Stressful Life Events and Cognitive Disorders in Central Africa
Neuroepidemiology 2015;44:99–107 DOI: 10.1159/000375462
Other Data Collected All covariates were collected during the first phase. Sociodemographic data included age, sex, marital status, formal education, country (CAR; ROC) and area (urban; rural). Age was ascertained from official documents using historical events [21] or from an informant if previous methods were unsuccessful. Body mass index (BMI) was used as a categorical variable consisting of three modalities:
