Abstract
INTRODUCTION
Dementia is a global public health problem of epidemic proportions. At present, 46.8 million people worldwide are living with dementia and this number will almost double every two decades, reaching 74.7 million in 2030 and 131.5 million in 2050; global costs of dementia have increased by 35.4% from US$ 604 billion to US$ 818 billion over the past five years [1]. Epidemiological studies have identified psychosocial, lifestyle, and vascular factors as modifiable risk and protective factors of mild cognitive impairment (MCI) and dementia [2–4] which are now broadly subsumed under the umbrella term of Neurocognitive Disorders (NCD) in the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5) [5]. In the new system, cognitive impairments that do not reach the threshold for a diagnosis of dementia are termed mild NCDs, whereas the dementias constitute nearly all of the major NCDs.
Psychosocial factors and interactions are of particular relevance to social policies and planning for aging societies. In earlier studies, indicators of social isolation such as living alone, loneliness, being married, and levels of social engagement have been linked to late life cognitive impairment [4, 6–9]. The Kungsholmen project found that those who are single or living alone had a higher risk of incident dementia [8]. On the other hand, other studies reported that feelings of loneliness, but not social isolation, predict dementia onset. [6] Studies of European populations reported that single or never married individuals were found to have an increased risk of dementia [8, 11]. These studies do not all identify consistent associations between various indicators of social engagement and cognitive impairment [12]. Life satisfaction is a self-perceived level of psychological well-being that is advocated as an important measure of societal well-being [13]. An overall low level of life satisfaction in cognitively healthy older adults is also reported to predict dementia [14]. Evidence suggests there are gender differences in the effect of marital status on health outcomes [15, 16] and being married has been found to have a positive association with life satisfaction especially for males [17]. These inter-related psychosocial measures (living alone, loneliness, being married, and life satisfaction) reflect exogenous sources of psychological stress and socio-emotional adaptation that may have net positive or negative effects on the likelihood of developing neurocognitive disorders. To our knowledge, they have not been investigated together in the same study to determine their independent effect in predicting the risk of neurocognitive disorders.
In this study, we investigate the associations of living alone, loneliness, being married, and life satisfaction with the development of incident MCI-and-dementia in a population cohort. We hypothesize that whereas living alone and marital status are social factors representing social isolation, loneliness, and life satisfaction may represent underlying psychological factors that directly contribute to the risk of cognitive impairment and neurocognitive disorder. Given their inter-relatedness, one or more of these factors are independently associated with the increased risk of developing MCI and/or dementia when the presence of the other psychosocial factors are taken into account and controlled for in the analysis. There may also be possible interactions between these psychosocial factors.
METHOD
Study population
Between September 2003 and December 2005, a whole population of older adults aged 55 years and above who were Singaporean residents in a geographically defined area in the South East region of Singapore were identified from a door–to–door census and invited to participate in the Singapore Longitudinal Ageing Study (SLAS-1). All participants provided written informed consent. The study was approved by the Institutional Review Board of National University of Singapore. Full details of the survey procedures and baseline study variables and data collection are described in previous publications [18].
Baseline information on demographic variables, medical history, physical function, and mental health status were collected from face–to–face interviews conducted by trained nurses using structured questionnaires at the participants’ home. Longitudinal follow up of diagnoses of MCI and dementia was conducted for up to 8 years. In this study, we analyze data from 1601 cognitively normal participants who were free of MCI or dementia at baseline and with complete information on cognitive outcomes at follow up.
Neurocognitive assessment and diagnosis
Details of the procedures and workflow for the diagnoses of MCI and dementia have been described in a previous paper [19] and summarized in the Flowchart (Fig. 1). Briefly, at baseline and at two follow-ups 3 to 4 years apart, the presence of cognitive impairment was screened using a modified version of the Mini-Mental State Examination (MMSE) [20] using cutoff of 27 and below, and the Clinical Dementia Rating Scale (CDR) [21] performed by trained research nurses. Detailed neuropsychological assessment was performed with a battery of neuropsychological tests by psychologists. Cases of incident neurocognitive disorder identified by a global CDR score of 0.5 and above were reviewed by a consensus panel consisting of geriatricians, psychiatrists, and psychologists before assigning the diagnosis of neurocognitive disorder. MCI was defined according to Petersen’s criteria [22, 23], and dementia diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 4th revised edition criteria for dementia syndrome [24].
Cognitive decline was determined from baseline and follow up values of MMSE, using Singaporean population-based conditional age- and education- standardized norms for assessing changes in MMSE scores that takes into account prior MMSE score and interval years for assessing longitudinal change [25]. Cognitive decline is deemed to be present when the observed MMSE value at follow up was below the 50% percentile value estimated for the individual’s age, education, prior MMSE score and interval years between MMSE measurements. This is more precise than using crude “ballpark” figures (typically 1 or 2 points or more of MMSE drop annually), which generally ignore younger or older age of the patient, and do not consider age and education specific change norms.
Psychosocial variables
Living arrangement and marital status
Respondents were asked during baseline assessment “Who do you live with?” The close–ended responses include (1) live with spouse, son, daughter, grand–children, other relatives or friends or others, (‘living with others’) or (2) ‘live alone’. Marital status was ascertained and close ended responses included (1) single or (2) married or (3) divorced, separated or (4) widowed.
Loneliness
Sense of loneliness was measured by asking participants “Do you feel that at the present moment you are (1) not at all lonely or (2) fairly lonely or (3) very lonely”.
Life satisfaction
Overall positive life satisfaction was determined using a self-reported Life Satisfaction Scale comprising four questions that assessed the subjects’ interest in life, happiness, loneliness, and general ease of living, which has been shown to predict mortality [26]. Respondents rated whether they find life “interesting or boring,” “happy or sad,” or “easy or hard” on a 5-point Likert scale (such as 1 “very interesting” to 5 “very boring”), or “lonely” (3-point Likert scale: 1 not at all, 2 fairly lonely, 3 very lonely). For ease of analyses, responses of “very happy”, “very interesting”,“very lonely” and “very easy” were each given a score of 1 such that the total score ranged from 0 to 4, with a higher score indicating higher life satisfaction. a participant was considered to be “very satisfied” if the summed score was 2 and above.
Covariates
Covariates include socio-demographic variables (age, gender, and education), lifestyle and habits (cigarette smoking, alcohol consumption), chronic medical conditions, depression, and APOE4 allele status. The Geriatric Depression Scale (GDS) [27], which has been validated locally [28], was administered as a measure of depressive symptoms. APOE genotyping was determined by standardized laboratory techniques utilizing polymerase chain reaction amplification followed by restriction endonuclease digestion of the PCR product. Leisure-time activity was assessed by the usual number and frequency in 16 different categories of physical, social, or productive leisure activities, which were commonly performed by local older adults, using the same approaches for quantifying the level of leisure activity used in previous studies [18, 29–31]. The frequency of participation in each category of activities was measured on a 3-point Likert scale (0 = never or less than once a month; 1 = sometimes, i.e., once a month or more but less than once a week; 2 = often, i.e., at least once a week). The combined scores, with higher scores representing increasing levels of participation, were computed from the number and frequency of participation for all categories of activities and divided into tertile categories [18].
Medical conditions
Information on medical conditions was obtained from a self–reported history of medical conditions diagnosed by a doctor and corroborated by the report of specific drugs, diagnostic or interventional procedures, and laboratory test results. The presence of hypertension was defined by self–report of hypertension with anti–hypertensive medication use, or blood pressure measurement (untreated hypertension: systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg); diabetes mellitus was defined by self–report of diabetes on anti–diabetic medications, or by elevated fasting blood sugar (untreated diabetes: fasting blood glucose ≥7.0 mmol/L); central obesity defined as waist circumference of ≥90 cm and ≥80 cm for Asian men and women respectively; stroke from self-report of stroke or transient ischemic attack; heart disease from self-report of myocardial infarction, atrial fibrillation and congestive heart failure, ECG evidence and/or use of appropriate medications, or interventional procedures; lipid abnormalities from self-report of high cholesterol and use of lipid lowering drugs or abnormal lipid panel results (Total cholesterol ≥6.5 mmol/L or low density lipoprotein (LDL) ≥4.1 mmol/L or triglyceride (TG) ≥2.3 mmol/L or high density lipoprotein (HDL) <1.0 mmol/L) [32].
Statistical analysis
Descriptive statistics were means (standard deviations) and numbers (proportions), which were compared using analysis of variance (ANOVA) for continuous variables and chi-squared tests for categorical variables. Univariate and multivariate Cox proportional hazard regression analyses with testing of proportional hazard assumption were used to estimate hazard ratio (HR) with 95% confidence intervals (95% CI) of incident MCI-dementia associated with psychosocial variables (marital status, living alone, loneliness, and life satisfaction score) as primary predictor variables, and included as covariates, age, sex, education, ethnicity, smoking status, APOE4 allele carrier status, cardiovascular and related risk factors (dyslipidemia, hypertension, diabetes, central obesity, history of stroke or heart disease, depression, and current alcohol use), and lifestyle behavioral variables (physical activities score, social activities score, productive activities score, and leisure time total score). Stepwise analyses were performed for multiple covariates (Model 1: base model variables were age (in years), sex, secondary and above education, ethnicity, smoking, alcohol, dyslipidemia, hypertension, diabetes, central obesity, history of stroke or heart disease, APOE-ɛ4 allele carrier, depression (GDS ≥5), physical activities (FAS) tertile score, social activities (SAS) tertile score, productive activities (PAS) tertile score; Model 2: base model variables and all other psychosocial variables). We also explored possible statistical interactions between marital status and gender, and marital status and life satisfaction. Further analyses with univariate and multivariate logistic regression was conducted to explore these psychosocial variables’ association with the risk of cognitive decline based on changes in MMSE global cognition. All analyses were conducted using IBM Statistical Package for the Social Sciences (SPSS version 20) software.
RESULTS
The participants at baseline consisted of 118 (7%) who lived alone, 285 (18%) who felt lonely, 1,197 (75%) who were married, and 379 (24%) who were very satisfied with their life. The non-married individuals comprised 95 (5.9%) who were single, 60 (3.7%) who were divorced, and 249 (15.6%) who were widowed. Sociodemographic, lifestyle, and vascular variables that are known to be associated with the risk of MCI/dementia of the participants are described in Table 1. The psychosocial variables were strongly correlated with one another, with the exception of living alone which was not associated with being satisfied with life.
A total of 163 out of 1,601 cognitively healthy participants converted to MCI-dementia over 5,420 persons-years of follow up, giving an incidence of 3.01 per 100 person-years. (Table 2). The incidence of MCI/dementia was higher in participants who lived alone or experienced loneliness, and lower among those who were married, or were very satisfied with their life. In univariate analyses, individual HRs of associations with incident MCI-dementia were significant for living alone (1.86 [1.18–2.95], p = 0.008), being married (0.54 [0.39–0.75], p < 0.0001) and being very satisfied with life (0.59 [0.38–0.91]), p = 0.017) (Table 2), but not with feeling of loneliness (HR = 1.26 [0.86–1.84], p = 0.23).
In multivariate analyses, adjusting for age, sex, education, ethnicity, smoking, alcohol, dyslipidemia, hypertension, diabetes, central obesity, history of stroke, heart disease, APOE-ɛ4 allele carrier, depression, physical, social, and productive activities, living alone (HR = 1.64 [1.02 –2.63], p = 0.041) remained significantly associated with a higher risk of MCI-dementia, and being married (HR = 0.66 [0.46 –0.94], p = 0.019) and being very satisfied with life (HR = 0.63 [0.40 –0.99], p = 0.044) remained significantly associated with lower risks of developing MCI-dementia. However, when adjusted mutually for other psychosocial variables, in addition to above variables, living alone was not significantly associated with increased risk of MCI-dementia; only being married and being very satisfied with life remained significantly associated with reduced risk of MCI-dementia (Model 2, Table 2). Notably, there was no significant interaction between gender and marital status or marital status and life satisfaction.
We further explored whether these relationships were consistent when the various indicators of social isolation were analyzed for their associations with the risk of cognitive decline based on changes in MMSE global cognition. a total of 433 (27.0%) participants showed cognitive decline. The results shown in Table 3 are supportive of the independent association of being very satisfied with life with lower likelihood of experiencing cognitive decline, allowing for the presence of the other psychosocial variables. However, being married did not remain significantly associated with a lower risk of cognitive decline after adjusting for the presence of lifestyle, behavioral, and vascular risk factors, and other psychosocial variables.
DISCUSSION
Our results suggest that individuals who were married and who were very satisfied with life were protected against the risk of developing MCI-dementia. These findings are consistent with studies in European populations where conversely single or never married individuals were found to have an increased risk of dementia [8, 11]. Existing evidence suggests the effect of marital status on many health outcomes are variable depending on factors such as sex, with many showing men to benefit more from marriage [15, 16]. Our results did not indicate any gender differences in the effect of marital status on incident MCI-dementia. However, the observed association of being married with a lower risk of MCI-dementia was not consistently supported through its observed association with cognitive decline. Similar to our findings on life satisfaction, a recent Canadian study also found overall low life satisfaction in cognitively healthy older adults was associated with an increased risk of dementia from follow up [14]. Life satisfaction thus appears to be the most robust psychosocial factor that predicts a lower likelihood of cognitive decline and neurocognitive disorder, independently of marital status, living arrangement and loneliness.
We found that living alone was not associated with increased risk of MCI-dementia, independently of the other psychosocial variables. Past research evaluating living arrangements and cognitive impairment have yielded inconsistent results. Fratiglioni and colleagues found living alone was associated with increased risk of dementia [8]. Contrary to this finding, a study of participants from the National Alzheimer’s Coordinating Center database in the United States found living alone was not associated with an increased risk [33]. The AMSTEL study found that, rather than living alone, it was the feeling of loneliness that contributed to an increased risk of dementia [6].
When controlling only for the effects of demographic, lifestyle and vascular variables, living alone was observed in this study to be associated with the risk of MCI-dementia. This association was lost when there was further adjustment for the other psychosocial variables under study— marital status, loneliness and life satisfaction. We infer that this association was lost due to the fact that very few of those living alone were married, 14.4% compared to 79.6% among those who lived with others. Although more of those who lived alone felt lonely, feeling lonely was not a predictor of incident MCI-dementia. Living arrangement is not a consistent surrogate measure of social isolation across different populations [34]. Older persons who live alone may be more likely to be a self-selected population of those who are in good health and independent in their daily living activities. Indeed in this study, equal numbers of those who lived alone and those who lived with others were very satisfied with their lives.
A high level of life satisfaction, on the other hand, was found to be a strong predictor of the risk of incident MCI-dementia. This was notwithstanding the fact that the measure of life satisfaction encompassed loneliness as one domain, interest in life, happiness, and general ease of living being the other domains. Since loneliness on its own was not predictive of subsequent incident MCI-dementia, the other domains of life satisfaction clearly showed the effect of protecting older individuals from developing MCI or dementia.
This study has its limitations. Our study could have possibly missed incident MCI/dementia cases from the longer follow up interval. MCI cases may revert to normal cognition as well as progress to dementia.There were undetected cases of this changeable pre-dementia condition, as suggested by the fact that among these cognitively normal subjects, there were 13 cases of dementia who were diagnosed without prior detection of MCI status during the follow up.
As mentioned above, living arrangement as a proxy measure of social engagement and support was ostensibly not adequate, as this does not include the type, amount, or quality of social contacts. Although being married was shown to strongly predict a lower likelihood of developing neurocognitive disorder, marital status also does not measure the quality of spousal relationships. Future studies should investigate the various factors that influence social connectedness and quality of relationships and its associations with cognitive and health outcomes.
There is the possibility that changes in social engagement, loneliness, or life satisfaction may be a prodromal phase of dementia [35], hence obscuring the etiological relationship between them. However, in this study, the participants at baseline were cognitively normal and free of MCI prior to follow up. The participants also had a long follow up duration of up to eight years for observing incident cases of MCI and dementia.
The regression models were robust as multiple covariates including age, gender, education, APOE4 allele carrier status and chronic medical conditions, which are known risk factors of cognitive decline, were included to control for possible confounding. Nonetheless, there is possible residual confounding. We did not adjust for other measures of socio-economic status such as income or housing status because it is not widely established as a strong independent determinant of cognitive decline or dementia given its strong correlation with education. In addition, we were not able to analyze education based on the number of years of schooling and dichotomizing an important covariate may have led to under-adjustment for confounding. However, it is arguable if years of schooling sufficiently represents the quality of education, a more important factor.
Our findings are especially relevant for many Asian populations undergoing rapid demographic and socio-cultural changes in the face of projections that vast numbers of older persons will develop dementia. There is a paucity of Asian studies evaluating psychosocial factors influencing older people’s mental health including cognitive impairment and dementia. In this regard, our results underline the need to be cognizant of the role of psychosocial factors in cognitive health, and proactive preventive actions should address psychosocial factors as assiduously as lifestyle and vascular risk factors. Psychosocial interventional measures may have more tangible impact from targeting protective factors rather than risk factors. Alternatively to reactive measures aimed at reducing the psychological stress of social isolation, proactively enhancing psychological wellbeing and life satisfaction through greater social engagement and activity may have more visibly positive impacts. In a multi-sectoral action framework, living environments or urban spaces which are elder friendly in drawing older persons into community spaces and activity centers are but one example of psychosocial interventions that could have more extensive impact on improving cognitive health. Further research is needed to understand the roles of more specific psychosocial factors and the impact of interventions in lowering the risk of neurocognitive disorders.
Footnotes
ACKNOWLEDGMENTS
The study was supported by research grants from the Agency for Science Technology and Research (A*STAR) Biomedical Research Council (BMRC) [Grants: No. 03/1/21/17/214, 08/1/21/19/567] and from the National Medical Research Council [Grant: NMRC/1108/2007].
The study was approved by the Institutional Review Board of the National University of Singapore We thank the following voluntary welfare organizations for their support: Geylang East Home for the Aged, Presbyterian Community Services, St Luke’s Eldercare Services, Thye Hua Kwan Moral Society (Moral Neighbourhood Links), Yuhua Neighbourhood Link, Henderson Senior Citizens’ Home, NTUC Eldercare Co-op Ltd, Thong Kheng Seniors Activity Centre (Queenstown Centre) and Redhill Moral Seniors Activity Centre.
