We used a population based design with participants from two regions in eastern Finland. Participants were examined in mid-life (mean (SD) age 50.4 (6.0) years) and then again around 21 years later. The main variables were marital status (married/cohabiting, single, divorced, or widowed) measured at mid-life and follow-up and additional diagnostic measures of cognitive impairment (mild cognitive impairment, Alzheimer’s disease, and other forms of dementia) at follow-up. By combining marital status at both times, we created several categories of marital transition (such as married at both times, married in mid-life and widowed later in life, etc). We then related mid-life marital status and transitions in marital status from mid-life to later life to cognitive status later in life. We adjusted the estimations of these associations for several other variables from the mid-life measurements. Finally, we investigated if carriers of the apolipoprotein E e4 allele, the most important currently known genetic risk factor for Alzheimer’s disease, were especially at risk for cognitive impairment later in life if they also lived alone after losing their partner.
This research was part of the cardiovascular risk factors, aging and dementia (CAIDE) study. The participants of the CAIDE study comprised a random sample of 2000 survivors from four separate population samples, originally investigated in 1972, 1977, 1982, or 1987. These investigations assessed cardiovascular risk factors within the North Karelia Project and the FINMONICA study. The four original samples were randomly drawn from the population register of two regions in eastern Finland and comprised 30
078 participants aged 30-59. Each original sample was stratified so that there were at least 250 participants from each sex and from each of the three 10 year age intervals. The participation rate in the baseline investigations was 82-90%.
By the end of 1997, 2000 randomly selected survivors, all from or nearby the cities of Kuopio and Joensuu and aged 65-79, were invited for re-examination during the following year. The mean follow-up time was 20.9 years (SD 4.9). Altogether 1449 (73%), then aged 65-80 (mean age 71.3, SD 4.9), were able to or agreed to participate. This sample constitutes the database for the present study, together with the data from the baseline measurements and register linked data from later in life for the 551 non-participants. Figure 1 shows details of the flow of participants.
Fig 1 Flow of participants (MMSE=mini-mental state examination)
There were few differences between participants and non-participants at mid-life.28
Non-participants were somewhat older and less educated, had higher cholesterol concentration, blood pressure, and body mass index, and fewer of them did office or service work. Fewer were married or cohabiting (73.5% v
79.9% for participants).
The survey methods used during baseline (mid-life) examinations complied with the WHO MONICA protocol, described in more detail elsewhere.29
In brief, the baseline survey included a self administered questionnaire on health behaviour, health status, signs of depression, and medical history. Trained nurses checked the questionnaires to ensure that they were fully completed and understood. Participants’ blood pressure, height, and weight were measured, and body mass index calculated. A venous blood specimen was taken to determine serum cholesterol concentration. A questionnaire classified marital status into four categories: married/cohabiting, separated/divorced, single, or widowed.
Later life measurements
During the re-examination in 1998, the survey methods followed those applied in the previous surveys in all aspects. In addition, we identified participants’ apolipoprotein genotype by using polymerase chain reaction and Hhal digestion, as described by Tsukamoto et al.30
Cognitive status was assessed with a three step protocol for the diagnosis of dementia: a screening phase, a clinical phase, and a differential diagnostic phase. The 294 participants who scored 24 or less on the mini-mental state examination (MMSE)31
were referred for further examinations, including thorough neurological, cardiovascular, and neuropsychological assessments. Those with possible dementia, based on these assessments and as judged by an expert board, were referred to the differential diagnostic phase, including magnetic resonance imaging of the brain. In the final step, the review board re-analysed all data from the three phases before establishing the final diagnosis. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders
, 4th edition (DSM-IV), criteria in 57 participants. The diagnostic criteria for Alzheimer’s disease was fulfilled in 48 of these according to criteria from the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association.32
All patients with a diagnosis of Alzheimer’s disease showed generalised or medial temporal lobe atrophy, or both, without relevant vascular pathology, as revealed by magnetic resonance imaging. Mild cognitive impairment was diagnosed in 82, according to a procedure previously described,29
derived from the criteria advised by the Mayo Clinic Alzheimer’s disease research centre.33
The main criteria were objective impairment below 1.5 SD of the age appropriate mean in either memory or one other area of cognitive functioning, along with memory complaints. Marital status was determined by the same procedure as in mid-life.
We collected data on diagnoses of dementia in the 551 non-participants from local hospitals and healthcare centres. The total number of cases increased to 113 (5.9% of the population) when we took these diagnoses into account. As we lacked information on diagnosis procedures, apolipoprotein, and late marital status, we used this group only for reference to cross validate main results.
Directly relating the four categories of marital status in mid-life to all categories of cognitive impairment resulted in unacceptably low numbers of participants in some of the cells. Because we were interested in whether the reason for living without a partner would make any difference, in addition to collapsing the three non-cohabiting categories into one—that is, comparing cohabitants with non-cohabitants in mid-life—we used three categories: living with a partner, single/divorced, or widowed. This choice was based on theoretical and statistical considerations. Being widowed is the result of a traumatic, imposed, and involuntary marital transition that distinguishes it from the other two non-cohabitating categories (single and divorced). This assumption was reinforced by preliminary analyses that revealed a linear relation with the risk of cognitive impairment (measured by χ2 and logistic regressions) so that widowed people had the highest risk, single and separated or divorced people emerged as a middle category, and married people had the lowest risk (see table 2).
Table 2 Differences between marital status groups at mid-life in participants from Kuopio or Joensuu, Finland. Figures are means (SD) unless stated otherwise
By combining marital status in mid-life and later life, 13 theoretically possible categories of marital transition emerged (table 1). Based on these, we classified marital transition as cohabiting with a partner on both occasions, cohabiting with a partner in mid-life but not in later life, and living without a partner on both occasions. (The fourth category, living without a partner in mid-life but cohabiting in later life contained too few people to be used in calculations and it was not possible to combine it with any other category.) We performed separate calculations with this variable treated either as nominal or ordinal. The ordinal assumption was that each of the three categories should be associated with different amounts of time spent in a cohabiting partner relation from mid-life onwards.
Table 1 Marital status transitions* between mid-life and follow-up
Cognitive impairment was first treated as an “all inclusive” variable, comprising the 139 participants with a diagnosis of mild cognitive impairment or any kind of dementia. For more detailed analysis, we analysed mild cognitive impairment and Alzheimer’s disease separately. In each of the three analyses, the 1270 participants without any signs of cognitive impairment served as reference. In alternative calculations we entered cognitive function as ordinal, assuming that mild cognitive impairment represents a milder form of impairment than Alzheimer’s disease.
We used logistic regression to analyse the association between marital status and cognitive status later in life. Apart from adjustment for variables of most obvious relevance to predict dementia, such as age, apolipoprotein E e4 status, and education, we decided to adjust only for those variables for which we had data for all, or almost all, of the 1449 participants who were screened for dementia. Among these, we identified several variables related to marital status (table 2). Two further variables were selected for their contribution to the regression model after adjustments—namely, blood pressure and residence area. In the case of multicollinearity, we chose the variable that contributed most in the regression model. Because of this criterion, we chose age at follow-up instead of follow-up time and systolic blood pressure rather than diastolic blood pressure.
All the analyses were adjusted for age (at re-examination), education, sex, and apolipoprotein E e4 status (e4 carriers v non-carriers). In the next step we additionally adjusted for mid-life systolic blood pressure, cholesterol concentration, body mass index, smoking, occupation (farming/forestry as reference), region of residence, occupational physical activity, and signs of depression.
Each step of adjustment added significantly to explain the total variance in the regression model. Because progressive adjustments did not significantly change the association studied, we have presented only the final models, including all the adjustments.