Helsinki Birth Cohort Study Research Articles

The utilization of specialized healthcare services among frail older adults in the Helsinki Birth Cohort Study

Background The association between frailty and specialized healthcare utilization is not well studied. We, therefore, examined the utilization of specialized healthcare services among frail Finnish older adults. Methods A sub-sample of 1060 participants of the Helsinki Birth Cohort Study were followed prospectively for specialized healthcare utilization from nationwide registers between the years 2013 and 2017. The participants’ frailty status was assessed according to Fried’s criteria at a mean age of 71.0 (2.7 SD) years between the years 2011 and 2013. A negative binomial regression model was used to examine the association between frailty and the total number of visits, emergency visits, outpatient appointments separating the first outpatient appointments and the follow-up appointments, inpatient care including elective and non-elective hospital admissions and the total number of hospital days. We also calculated average length of stay (ALOS) and used the Kruskal–Wallis test to examine the differences between the groups. Results After adjusting for covariates, frailty was significantly associated with the number of specialized healthcare visits (IRR 1.50, 95% CI = 1.04–2.15) and all subgroups of visits apart from follow-up outpatient appointments. Frailty was particularly strongly associated with the number of hospital days (IRR 5.24, 95% CI = 2.35–11.7) and notably with emergency visits (IRR = 2.26, 95% CI = 1.45–3.51) and hospital admissions (IRR 2.23, 95% CI = 1.39–3.56). Frail older adults had also higher ALOS compared to non-frail participants (p = .009). Conclusions Frailty increases the use of most specialized healthcare services. Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems. KEY MESSAGE Frailty is associated with the utilization of most specialized healthcare services, the most expensive part of the healthcare in most high-income countries. The association of frailty with inpatient care is particularly strong. Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems.

Maternal body mass index, change in weight status from childhood to late adulthood and physical activity in older age

This study aimed to examine the longitudinal associations of maternal body mass index (BMI), weight status in childhood and late adulthood and device-measured total physical activity (TPA) in older age. The study involves 552 participants from Helsinki Birth Cohort Study who were born in Helsinki, Finland, in 1934-1944. TPA was measured with a multisensory body monitor at a mean age of 70years and expressed in metabolic equivalent of task hours/day (METh/d). Childhood overweight (BMI>85th percentile) was based on school health records at 6-7years of age, and late adulthood overweight (BMI≥25kg/m2 ) was based on clinical measurements at the mean age of 61years. Childhood overweight was associated with lower TPA, particularly in older women (mean difference -3.2 METh/d, 95% confidence interval (CI) -4.6 - -1.9), and late adulthood overweight was associated with lower TPA both in older women (mean difference -6.2, 95% CI (-7.2 - -5.1) and in older men (mean difference -2.6 METh/d, 95% CI -3.7 - -1.5). TPA in older age was highest in participants who were normal weight both in childhood and adulthood and lowest in participants who were overweight in childhood and adulthood. In participants with childhood overweight, TPA was lower in participants who were overweight both in childhood and adulthood compared to those who were overweight only in childhood. There was a U-shaped distribution of TPA according to maternal BMI in older women (P=.002), but not in older men. In conclusion, reaching normal weight after childhood predicted higher physical activity levels in older age.

Impaired glucose regulation, depressive symptoms, and health-related quality of life

IntroductionThis study aims to investigate whether the associations between impaired glucose regulation and health-related quality of life are modified by severity or type of depressive symptoms.Research design and methodsFor this...

Early exposure to social disadvantages and later life\xa0body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

BackgroundThe study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI.MethodsWe studied participants of Helsinki Birth Cohort Study born in 1934–1944 (HBCS1934–1944, n = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n = 5807, NFBC1986, n = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934–1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex.ResultsThe association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (β = 0.79, 95% CI, 0.33, 1.25, p < 0.001) in NFBC1966. In NFBC1986 this association was attenuated by PRS BMI (p = 0.181), and in HBCS1934–1944 there was no association between high early social disadvantage and increased later life BMI (β 0.22, 95% CI –0.91,1.35, p = 0.700). In HBCS1934–1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (β − 1.34, [− 2.37,-0.31], p = 0.011; β − 0.46, [− 0.89,-0.03], p = 0.038, respectively).ConclusionsHigh social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.

Blood pressure load per body surface area is higher in women than in men.

Many unexplained sex differences have been observed in blood pressure (BP) related morbidity. However, there has been little research about the most obvious difference between men and women-body size. Given that blood vessels are organs of tubular shape, we hypothesized that correction of BP for body surface area (BSA), a two-dimensional measurement of body size, would allow comparison of BP load between men and women. We assessed the relationship of 24-h ambulatory BP measurements and BSA in 534 participants (mean age 61 ± 3 years, 51% women) from the Helsinki Birth Cohort Study. The study subjects had no previous medication affecting vasculature or BP. When BP values were adjusted for age, smoking, physical activity, and body fat percentage, males had higher ambulatory daytime mean systolic BP (131 mmHg vs. 127 mmHg, p < 0.001), diastolic BP (83 mmHg vs. 78 mmHg, p < 0.001), and mean arterial pressure (100 mmHg vs. 96 mmHg, p < 0.001) than females. However, all BP components per unit of BSA were significantly lower in males: daytime mean systolic BP (65 mmHg vs. 71 mmHg, p < 0.001), diastolic BP (41 mmHg vs. 44 mmHg, p < 0.001), pulse pressure (24 mmHg vs. 28 mmHg, p = 0.013), and mean arterial pressure (49 mmHg vs. 54 mmHg, p < 0.001). The same phenomenon was observed in night-time BP values. BP load per BSA is higher in women than in men, which may explain many reported sex differences in cardiovascular morbidity. Relatively small-sized individuals might benefit from a more aggressive therapeutic strategy.

Body composition and changes in health-related quality of life in older age: a 10-year follow-up of the Helsinki Birth Cohort Study

Purpose Most studies examining the associations between body composition and health-related quality of life (HRQoL) in older age have been cross-sectional and analyzed only fat or lean mass. Hence, it is poorly known whether fat and lean mass are independently associated with subsequent changes in HRQoL. We investigated whether baseline lean and fat mass are associated with changes in HRQoL over a 10-year period in older adults.MethodsWe studied 1044 men and women from the Helsinki Birth Cohort Study (age 57–70 years at baseline). Bioelectrical impedance analysis was used to derive baseline fat mass index (FMI, fat mass/height2) and lean mass index (lean mass/height2), dichotomized at sex-specific medians. HRQoL was assessed using RAND 36-item Health Survey at baseline and follow-up 10 years later.ResultsWhen controlled for lean mass and adjusted for potential confounders, high baseline FMI was associated with a greater decline in general health (standardized regression coefficient [β] = − 0.13, p = 0.001), physical functioning (β = − 0.11, p = 0.002), role physical (β = − 0.13, p = 0.003), vitality (β = − 0.08, p = 0.027), role emotional (β = − 0.12, p = 0.007), and physical component score (β = − 0.14, p < 0.001). High baseline FMI was also associated with low HRQoL in all physical domains at baseline (β: from − 0.38 to − 0.10). Lean mass was not strongly associated with HRQoL at baseline or change in HRQoL.ConclusionIn older community-dwelling adults, higher fat mass is, independent of lean mass, associated with lower physical HRQoL and greater decline in HRQoL. Prevention of adiposity may contribute to preservation of a good quality of life in older age.

Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study

Background:Telomeres are crucial parts of chromosomes that protect the genome. They shorten every time the cell replicates, and shorter telomeres have been associated with increasing age and with many health behaviours. There is inconclusive evidence on the association between physical activity (PA) and telomere length. Objectives: To examine how leisure-time PA (LTPA) is associated with telomere length and telomere attrition during 10 years of follow-up in elderly people. Design: This study is a 10-year prospective follow-up study. Method: For this prospective study, we examined 1,014 subjects (mean age at baseline 60.8 years) from the Helsinki Birth Cohort Study (HBCS). Relative leukocyte telomere length (LTL) was measured with a quantitative real-time PCR and LTPA with a validated questionnaire. Multiple linear regression analyses were used to assess the association between sex-specific LTPA quartiles and LTL at baseline and change in LTL over 10 years. The analyses were adjusted for age, educational attainment, smoking, body fat percentage, oestrogen exposure in women and for follow-up time when applicable. Results: At baseline, volume of LTPA was not associated with LTL in men (p = 0.66) or in women (p = 0.33). Among women, however, higher volume of LTPA at baseline was associated with greater shortening of LTL (p for linearity 0.040) during the 10-year follow-up. No association was found among men (p for linearity 0.75). Conclusions: Our findings suggest that PA has a sex-specific role in regulation of telomere length in the aging process as in our study a high volume of LTPA in elderly women, but not in men, was associated with more rapid telomere attrition.

The impact of maternal weight in pregnancy on glucose metabolism in non-diabetic offspring in late adulthood

AimsWe aimed to examine the association between maternal adiposity and glucose metabolism in adult offspring without diabetes, simultaneous taking offspring own adiposity into account. MethodsThis longitudinal birth cohort study (Helsinki Birth Cohort Study) included 1,440 non-diabetic subjects examined at a mean age of 62 years. Subjects were divided into quartiles according to maternal body mass index (BMI). The impact of maternal BMI on offspring body composition was also studied. ResultsThere were no differences in fasting glucose between the groups. In men, maternal BMI was inversely associated with mean 2-hour glucose concentration after a 75 g oral glucose tolerance test (p < 0.001) and mean homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.049). According to the subjects’ own BMI, high maternal BMI was associated with lower 2-hour glucose concentrations only in non-obese men and with lower HOMA-IR only in obese men. Maternal BMI was not associated with glucose concentrations nor with HOMA-IR in women. In addition, maternal BMI was positively associated with a higher offspring lean body mass in men. ConclusionsHigh maternal BMI was associated with lower 2-hour plasma glucose concentration, especially in non-obese men. Offspring lean body mass may be a mediating factor for the association.

Telomere length and physical performance among older people—The Helsinki Birth Cohort Study

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001–2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011–2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

Change in physical activity and health-related quality of life in old age-A 10-year follow-up study.

The aim of the study was to examine the association between change in leisure-time physical activity (LTPA) and change in health-related quality of life (HRQoL) and symptoms of depression during a 10-year follow-up. This prospective study included 1036 men and women (mean age at baseline=61.2years) from the Helsinki Birth Cohort Study. Leisure-time physical activity was measured with a questionnaire, HRQoL with SF36 and depression symptoms with Beck's depression inventory (BDI). The association between the change in LTPA and change in HRQoL and BDI were investigated with sex-stratified general linear models adjusted for age, smoking, educational attainment, comorbidity score, and baseline value of outcomes. One standard deviation (SD) increase in LTPA was associated with increase in physical summary component of HRQoL in women (B=0.7 unit, 95% CI=0.1-1.3, P=0.032) and in men (B=0.8 unit, 95% CI=0.2-1.5, P=0.014). In women, the 1SD increase in LTPA was also associated with an increase in mental summary component score (B=1.0, 95% CI=0.3-1.7, P=0.005) and a reduction in depressive symptoms (B=-0.7, 95% CI=-1.1 to -0.2, P=0.003). In conclusion, increase in the volume of LTPA over a 10-year period in late adulthood was associated with improved HRQoL in both men and women, and also diminished depressive symptoms in women. The findings support the promotion of physical activity in later years to enhance HRQoL and mental well-being.

Physical heaviness of work and sitting at work as predictors of mortality: a 26-year follow-up of the Helsinki Birth Cohort Study

ObjectivesTo examine the relationships of late-career physical heaviness of work and sitting at work with mortality. A national-level job exposure matrix was used to determine the occupation-specific level of physical...

Associations of Fat and Lean Body Mass with Circulating Amino Acids in Older Men and Women.

Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62-74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.

The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood

Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934–1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65–77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31–0.58); B = 0.33 (95% CI = 0.20–0.46); B = 0.10 (95% CI = 0.01–0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.

Work careers in adults separated temporarily from their parents in childhood during World War II

IntroductionTraumatic experiences, such as separation from parents in childhood causing early life stress (ELS) may increase the risk of adverse long-term health outcomes and biological age-related changes. This may have an impact on work career. Our aim was to examine long term consequences of ELS due to temporary separation from parents during World War II (WWII) in relation to work career. Material and methodsThe Helsinki Birth Cohort Study comprises 13,345 individuals born in Helsinki, Finland, between the years 1934–1944. From the original cohort, 1781 individuals were identified as being separated temporarily from their parents due to World War II. Information on date and type of pension was provided by the Finnish Centre for Pensions and the Social Insurance Institution of Finland. The cohort members either transitioned into old age pension at the statutory retirement age or retired earlier and transitioned into disability, unemployment, part-time pension or died before retirement. ResultsThose who were separated were more likely to have transitioned into disability pension (RRR: 1.26: 95% CI: 1.06–1.48), especially due to diseases of the musculoskeletal system (OR: 1.57; 95% CI: 1.20–2.07), or into unemployment pension (RRR: 1.25; 95% CI: 1.02–1.53) compared with those not separated from their parents. Longer duration of separation was associated with early exit from the workforce compared with non-separation. ConclusionsExposure to ELS may have an impact upon lifetime work career. Early interventions preventing exposure to ELS or mitigating its negative effects may prolong future work careers along with healthier aging across the life-span.

Healthy diets and telomere length and attrition during a 10-year follow-up.

Telomeres are repeats of DNA that contain the sequence TTAGGG at the ends of each chromosome, and their function is to protect DNA from damage. Little evidence exists regarding the relationship between dietary patterns and telomere length, especially derived applying longitudinal design. The aim was to study if overall dietary pattern is associated with leukocyte telomere length (LTL) or faster telomere attrition or both. The setting was longitudinal and observational. Participants were 456 men and 590 women whose birth settled in between 1934 and 1944 and who participated in the Helsinki Birth Cohort Study. Baltic sea diet score (BSDS), modified Mediterranean diet score (mMED), and dietary inflammatory index (DII®) were calculated based on a 128-item food frequency questionnaire (FFQ) collected in 2001-2004. LTL was measured twice, in 2001-2004 and in 2011-2013 by quantitative real-time polymerase chain reaction. Association between the dietary patterns and LTL were analysed by general linear models with appropriate contrasts. BSDS, mMED, and DII did not associate with LTL in the cross-sectional analysis in men or women. Higher mMED at baseline (2001-2004) was associated with slightly faster LTL shortening during the follow-up (standardized ß -0.08, 95% CI -0.15, -0.01). No association between mMED and LTL change was found in men. Adherence to BSDS and DII did not associate with LTL change in men or women. Baltic sea diet, Mediterranean diet, and diet's inflammatory potential seem to have only little impact on telomere length and telomere attrition in elderly Finnish men and women.

Association between dog ownership and type 2 diabetes in later life: the Helsinki birth cohort study

ABSTRACT Dog ownership has been reported to have beneficial effects on physical activity and emotional well-being, both known to reduce the risk for type 2 diabetes (T2D). The aim of this study was to evaluate the association between dog ownership during the whole life course and having T2D in later life. The study subjects consisted of 731 people (307 men and 424 women) from the Helsinki Birth Cohort Study. We assessed dog ownership with questionnaires, for every decade of life as well as current dog ownership. We investigated the associations between dog ownership and T2D with generalised estimating equation models and with generalised linear models. At a mean age of 71.0 (standard deviation [SD] 2.6) years, 13% of the participants had T2D. Dog ownership prior to the clinical examination was not associated with T2D (p ≥ 0.51). In men, but not in women, current dog owners had greater odds of having T2D compared with the non-owners when adjusted for age when clinically examined, socio-economic status, smoking, leisure-time physical activity, chronic diseases (OR = 3.32, 95% confidence interval 1.25–8.79, p = 0.016). In the age group of people around 70 years, dog ownership is not associated with reduced odds for developing T2D. Abbreviations: BMI: body mass index; CI: confidence interval; GEE: generalised estimating equation; HBCS: Helsinki Birth Cohort Study; KIHD: Kuopio Ischemic Heart Disease; LTPA: leisure-time physical activity; MET: metabolic equivalent of task; OGTT: oral glucose tolerance test; OR: Odds ratio; SD: standard deviation; SES: socio-economic status; T2D: type 2 diabetes

Dog Ownership from a Life Course Perspective and Leisure-time Physical Activity in Late Adulthood: The Helsinki Birth Cohort Study.

Objective We investigated the association between dog ownership during the life course and leisure-time PA (LTPA) in late adulthood. Methods We included 714 participants (mean age = 70.8 ± 2.6 years) from the Helsinki Birth Cohort Study (HBCS). Dog ownership for every decade of life, current dog ownership, and current LTPA in metabolic equivalents of task (MET) were assessed with questionnaires. Age and sex adjusted generalized estimating equation models and analysis of regression were applied for the analyses. Results No significant age by dog ownership interaction on total, conditioning or non-conditioning LTPA was found (p ≥ .68). However, after the age of 40 years, dog ownership was increasingly associated with greater total and non-conditioning LTPA in later life. The mean difference in total LTPA, which was mostly explained by non-conditioning LTPA, was largest between the current dog owners and non-owners (15.2 MET-hours/week, 95% CI: 5.5-24.8, p = .002). ConclusionsCurrent dog ownership is associated with 15.2 MET-hours/week greater total LTPA compared to the non-owners. The differences were already observable after the age of 40. Thus, dog ownership induced increase in LTPA can have a positive influence on the aging processes and consequently positively influence healthy active aging.

The Healthy Nordic Diet and Mediterranean Diet and Incidence of Disability 10 Years Later in Home-Dwelling Old Adults

Background/ObjectiveDiet has a major impact on a person's health. However, limited information exists on the long-term role of the whole diet on disability. We investigated the association of the healthy Nordic diet and the Mediterranean diet with incident disability 10 years later. DesignLongitudinal, with a follow-up of 10 years. Settings/ParticipantsA total of 962 home-dwelling men and women from the Helsinki Birth Cohort Study, mean age 61.6 years, who were free of disability at baseline. MeasurementsAt baseline, 2001-2004, the Nordic diet score (NDS) and modified Mediterranean diet score (mMDS) were calculated using a validated 128-item food-frequency questionnaire. Higher scores indicated better adherence to the diet. Participants' incident disability was assessed during 2011-2013 by a self-reported questionnaire and was based on mobility limitations and difficulties to perform self-care activities. Analyses were performed using logistic regression and adjusted for potential confounding factors. ResultsIn total, 94 participants (9.8%) developed mobility limitations and 45 participants (4.7%) developed difficulties in self-care activities during 10 year follow-up. The likelihood of having mobility limitations (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.22–0.80) and difficulties in self-care activities (OR 0.38, 95% CI 0.15–0.94) were lower among those in the highest NDS tertile than among those in the lowest NDS tertile. Greater mMDS was associated with a lower disability incidence; however, the association was not statistically significant. Conclusions/ImplicationsAdherence to the healthy Nordic diet predicts 10-year incidence of mobility limitations and difficulties to perform self-care activities in old age and may thus be protective against disability in Nordic population.

Association of childhood adversities and home atmosphere with functioning in old age: the Helsinki birth cohort study.

childhood adversities have been linked with adverse health outcomes, but less is known about the long-term consequences of childhood home atmosphere. We investigated whether childhood adversities and home atmosphere were associated with physical and mental functioning in older age. in the Helsinki Birth Cohort Study 2003, participants born in the year 1934-44 had data available on nine childhood home atmosphere items, e.g. whether it was supportive and warm (sum score ranged between 0 and 36, higher score indicating better atmosphere), and nine childhood adversities, e.g. unemployment and divorce (sum score 0-9, coded into no; one; and two or more adversities) assessed in 2001-04. Of those, 835 had data on physical and mental functioning assessed using the Short Form 36 questionnaire in 2011-13. those who had experienced two or more childhood adversities were more likely to have poorer physical and mental functioning in older age compared to those with no adversities. A better home atmosphere score was associated with better mental functioning (per one unit higher score β 0.24, 95% CI 0.16-0.32, P < 0.001). In models including both childhood adversities and home atmosphere, a more favourable home atmosphere was associated with better mental functioning while the association for childhood adversities attenuated. There were no associations between childhood adversities or home atmosphere and physical functioning in the models that included both childhood exposures. childhood adversities and home atmosphere have long-term associations with physical and mental functioning in older age.

APOE ɛ4, rs405509, and rs440446 promoter and intron-1 polymorphisms and dementia risk in a cohort of elderly Finns-Helsinki Birth Cohort Study.

We tested if the ε4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms. APOE ε4 predicted higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI] 1.76, 7.70) across all statistical models, and when adjusted for rs405509 and rs440446. The number of minor alleles in rs405509 or rs440446 was not associated with dementia risk (hazard ratios<1.43; 95% CI 0.87, 2.36). As rs405509 or rs440446 has been associated with nonpathological cognitive aging in this and other cohorts independent of the APOE major isoforms, these findings lend credence that APOE locus may be linked with dementia risk and nonpathological cognitive aging via separate mechanisms.