Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

BACKGROUND AND OBJECTIVES: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear. METHODS: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19). Group-based trajectory modeling identified trajectories of occupational cognitive demands, measured by the routine task intensity (RTI) index (lower RTI indicates more cognitively demanding occupation) from the Occupational Information Network. Multinomial regression was implemented to estimate the relative risk ratios (RRRs) of MCI and dementia, after adjusting for age, sex, education, income, baseline hypertension, obesity, diabetes, psychiatric impairment, hearing impairment, loneliness, smoking status, and physical inactivity assessed at HUNT1-2 in 1984-1986 and 1995-1997. To handle missing data, we used inverse probability weighting to account for nonparticipation in cognitive testing and multiple imputation. RESULTS: Based on longitudinal RTI scores for 305 unique occupations, 4 RTI trajectory groups were identified (n = 7,003, 49.8% women, age range 69-104 years): low RTI (n = 1,431, 20.4%), intermediate-low RTI (n = 1,578, 22.5%), intermediate-high RTI (n = 2,601, 37.1%), and high RTI (n = 1,393, 19.9%). Participants in the high RTI group had a higher risk of MCI (RRR 1.74, 95% CI 1.41-2.14) and dementia (RRR 1.37, 95% CI 1.01-1.86), after adjusting for age, sex, and education compared with participants in the low RTI group. In a sensitivity analysis, controlling for income and baseline health-related factors, the point estimates were not appreciably changed (RRR 1.66, 95% CI 1.35-2.06 for MCI, and RRR 1.31, 95% CI 0.96-1.78 for dementia). DISCUSSION: People with a history of cognitively stimulating occupations during their 30s, 40s, 50s, and 60s had a lower risk of MCI and dementia older than 70 years, highlighting the importance of occupational cognitive stimulation during midlife for maintaining cognitive function in old age. Further research is required to pinpoint the specific occupational cognitive demands that are most advantageous for maintaining later-life cognitive function.

Health-promoting behaviors in older adulthood and intrinsic capacity 10 years later: the HUNT study.

BACKGROUND: With the global population growing older, there is a need for more knowledge of how to improve and/or maintain functional capacities to promote healthy ageing. In this study we aimed to assess the effect of several known health-promoting behaviors in old age with intrinsic capacity ten years later. METHODS: This was a prospective cohort study looking at participants that were ≥ 65 years at the time of the third wave of the Trøndelag Health Study (HUNT3, 2006-2008) who also took part in the 70 + sub-study of the fourth wave (HUNT4 70+, 2017-2019). Self-reported behavior data from short questionnaires, including diet and physical activity, were collected in HUNT3, and data on the five domains of intrinsic capacity defined by the World Health Organization were collected in HUNT4 70+. A composite index was created for both healthy life and intrinsic capacity, awarding points for how well participants adhered to guidelines for healthy living and their level of functional impairment, respectively. Ordinal logistic regression was used to assess the relationship between health-promoting behaviors and intrinsic capacity. RESULTS: Of 12,361 participants in HUNT3 ≥ 65 years, 4699 (56.5% women) also participated in HUNT4 70+. On the health-promoting behaviors, lowest adherence to healthy living guidelines were seen for fruit and vegetables intake (47.2%), milk intake (46.7%) and physical activity (31.1%). On intrinsic capacity domains, highest impairment was seen in the domains of locomotion (29.7%), hearing (11.1%) and vitality (8.3%). A higher adherence to guidelines for healthy living was associated with higher intrinsic capacity 10 years later. A one-point increase in the healthy life index was associated with a 1.15 (95% confidence interval 1.10-1.21) times increased odds of being in a higher intrinsic capacity category. CONCLUSION: Health-promoting behaviors in old age are associated with better intrinsic capacity ten years later. In clinical settings assessment of health-promoting behaviors could potentially be done using short questionnaires.

Trajectories of occupational physical activity and risk of later-life mild cognitive impairment and dementia: the HUNT4 70+ study.

Background: High levels of occupational physical activity (PA) have been linked to an increased risk of dementia. We assessed the association of trajectories of occupational PA at ages 33-65 with risk of dementia and mild cognitive impairment (MCI) at ages 70+. Methods: We included 7005 participants (49.8% were women, 3488/7005) from the HUNT4 70+ Study. Group-based trajectory modelling was used to identify four trajectories of occupational PA based on national registry data from 1960 to 2014: stable low (30.9%, 2162/7005), increasing then decreasing (8.9%, 625/7005), stable intermediate (25.1%, 1755/7005), and stable high (35.2%, 2463/7005). Dementia and MCI were clinically assessed in 2017-2019. We performed adjusted multinomial regression to estimate relative risk ratios (RRR) with 95% confidence intervals (CI) for dementia and MCI. Findings: 902 participants were diagnosed with dementia and 2407 were diagnosed with MCI. Absolute unadjusted risks for dementia and MCI were 8.8% (95% CI: 7.6-10.0) and 27.4% (25.5-29.3), respectively, for those with a stable low PA trajectory, 8.2% (6.0-10.4) and 33.3% (29.6-37.0) for those with increasing, then decreasing PA; while they were 16.0% (14.3-17.7) and 35% (32.8-37.2) for those with stable intermediate, and 15.4% (14.0-16.8) and 40.2% (38.3-42.1) for those with stable high PA trajectories. In the adjusted model, participants with a stable high trajectory had a higher risk of dementia (RRR 1.34, 1.04-1.73) and MCI (1.80, 1.54-2.11), whereas participants with a stable intermediate trajectory had a higher risk of MCI (1.36, 1.15-1.61) compared to the stable low trajectory. While not statistically significant, participants with increasing then decreasing occupational PA had a 24% lower risk of dementia and 18% higher risk of MCI than the stable low PA group. Interpretation: Consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment, indicating the importance of developing strategies for individuals in physically demanding occupations to prevent cognitive impairment. Funding: This work was supported by the National Institutes of Health (R01AG069109-01) and the Research Council of Norway (296297, 262700, 288083).

Change in physical activity and systolic blood pressure trajectories throughout mid-life and the development of dementia in older age: the HUNT study.

BACKGROUND: There is lack of research on combinations of possible modifiable risk factors for dementia in a life-time perspective. Dementia has currently no cure, and therefore new knowledge of preventive factors is important. The purpose of this study is to investigate if changes in physical activity (PA) in combinations with systolic blood pressure (SBP) trajectories in mid to late life are related to development of dementia in older age. METHODS: This prospective cohort study uses data from four consecutive surveys of the HUNT Study, Norway. Dementia was assessed in the HUNT4 70 + sub-study (2017-19). Group-based trajectory modelling identified three SBP trajectories from HUNT1 (1984-86) to HUNT3 (2006-2008): low, middle, and high. Change in PA was categorized into four groups based on high or low PA level at HUNT1 and HUNT3 and were combined with the SBP trajectories resulting in 12 distinct categories. Logistic regression was used to estimate odds ratios (ORs) of dementia. RESULTS: A total of 8487 participants (55% women, mean age (SD) 44.8 (6.5) years at HUNT1) were included. At HUNT4 70 + , 15.2% had dementia. We observed an overall decrease in OR of dementia across the PA/SBP categories when ranked from low to high PA (OR, 0.96; 95% CI, 0.93 to 1.00, P = 0.04). Within PA groups, a low SBP trajectory was associated with lower OR for dementia, apart from those with decreasing PA. The strongest association was observed for people with stable high PA and low SBP trajectory (OR, 0.38; 95% confidence interval (CI), 0.13 to 1.10 and adjusted risk difference, -8.34 percentage points; 95% CI, -15.32 to -1.36). CONCLUSION: Our findings illustrate the clinical importance of PA and SBP for dementia prevention and that favorable levels of both are associated with reduced occurrence of dementia.

Cardiorespiratory fitness and incident use of anxiolytics and antidepressants in adults. A linkage study between HUNT and the Norwegian Prescription Database.

BACKGROUND: We investigated the association between cardiorespiratory fitness (CRF) and incident use of antidepressants or anxiolytics in the general adult population. METHODS: A non-exercise prediction model was used to estimate CRF in 32,603 participants in the third wave of the Trøndelag Health Study (HUNT3; 2006-08). Data on first purchase of antidepressants and anxiolytics were obtained from the Norwegian Prescription Database. Cox regression was used to estimate hazard ratios (HRs). RESULTS: Each 1- metabolic equivalent of task (MET) increase in CRF was associated with 4 % reduced risk of purchasing antidepressant or anxiolytic medication during follow-up (HR 0.96, 95 % Confidence interval [CI] 0.94-0.98). Compared to the low CRF tertile, participants in intermediate (HR 0.93, 95 % CI 0.87-0.98) and high (HR 0.92, 95 % CI 0.86-0.98) CRF tertiles had reduced risk of medication purchase. Men in intermediate and high CRF tertile had lower risk of medication purchase (intermediate HR 0.87, 95 % CI 0.79-0.96; high HR 0.87, 95 % CI 0.78-0.96). Intermediate and high CRF tertiles were associated with reduced risk of medication use for younger adults (20 to <30 years old; intermediate HR 0.74, 95 % CI 0.61-0.91, high HR 0.78, 95 % CI 0.64-0.95) and middle-aged adults (30 to <65 years old; intermediate HR 0.90, 95 % CI 0.83-0.97, high HR 0.90, 95 % CI 0.84-0.98), but not in older adults (≥65 years old). LIMITATIONS: Only information about medication purchase and not actual use was available. CONCLUSION: Increased CRF is associated with reduced risk of anxiolytics and antidepressants purchase, with stronger effects for men and younger adults.

Retirement age and disability status as pathways to later-life cognitive impairment: Evidence from the Norwegian HUNT Study linked with Norwegian population registers.

BACKGROUND: Research shows that retirement age is associated with later-life cognition but has not sufficiently distinguished between retirement pathways. We examined how retirement age was associated with later-life dementia and mild cognitive impairment (MCI) for people who retired via the disability pathway (received a disability pension prior to old-age pension eligibility) and those who retired via the standard pathway. METHODS: The study sample comprised 7210 participants from the Norwegian Trøndelag Health Study (HUNT4 70+, 2017-2019) who had worked for at least one year in 1967-2019, worked until age 55+, and retired before HUNT4. Dementia and MCI were clinically assessed in HUNT4 70+ when participants were aged 69-85 years. Historical data on participants' retirement age and pathway were retrieved from population registers. We used multinomial regression to assess the dementia/MCI risk for women and men retiring via the disability pathway, or early (<67 years), on-time (age 67, old-age pension eligibility) or late (age 68+) via the standard pathway. RESULTS: In our study sample, 9.5% had dementia, 35.3% had MCI, and 28.1% retired via the disability pathway. The disability retirement group had an elevated risk of dementia compared to the on-time standard retirement group (relative risk ratio [RRR]: 1.64, 95% CI 1.14-2.37 for women, 1.70, 95% CI 1.17-2.48 for men). MCI risk was lower among men who retired late versus on-time (RRR, 0.76, 95% CI 0.61-0.95). CONCLUSION: Disability retirees should be monitored more closely, and preventive policies should be considered to minimize the dementia risk observed among this group of retirees.

Association Between Cardiorespiratory Fitness and Incident Purchase of Hypnotic Drugs in Adults: The HUNT Study.

OBJECTIVE: To assess whether cardiorespiratory fitness (CRF) is associated with first purchase of a prescribed hypnotic drug in the adult population. METHODS: A total of 34,357 adult participants (53.9% women) with a mean age of 51.5 years (SD 15.6 years) from the third Trøndelag Health Study (HUNT) of 2006 to 2008 were observed until January 1, 2018. Cardiorespiratory fitness was estimated from a validated nonexercise algorithm. Data on first hypnotics prescription were obtained through linkage to the National Norwegian Prescription Database. Cox regression with 95% CIs was used to estimate hazard ratios (HRs). RESULTS: After 304,899 person-years of follow-up, 5791 participants had their first registered purchase of prescribed hypnotics, corresponding to an incidence rate of 1.90 per 100 person-years. Each 1-metabolic equivalent of task increase in CRF was significantly associated with 5% (HR, 0.95; 95% CI, 0.91 to 0.99; P=.02) and 4% (HR, 0.96; 95% CI, 0.92 to 1.00; P=.046) risk reduction for incident use of hypnotics in men and women, respectively. When CRF was categorized into tertiles with lowest CRF as the reference group, reduced risk was 13% (HR, 0.87; 95% CI, 0.79 to 0.96; P=.006) and 15% (HR, 0.85; 95% CI, 0.77 to 0.95; P=.003) for men in the intermediate and highest CRF category, respectively. In women with highest CRF, the reduced risk was 5% (HR, 0.95; 95% CI, 0.87 to 1.03; P=.22). CONCLUSION: Cardiorespiratory fitness in adulthood is associated with incident purchase of prescription medication commonly used for sleep problems. These findings suggest that fitness should be considered a target for preventing sleep problems in adults.

Marital Histories and Associations With Later-Life Dementia and Mild Cognitive Impairment Risk in the HUNT4 70+ Study in Norway.

Objectives: Earlier studies suggest that being married in later life protects against dementia, and that being single in old age increases the risk of dementia. In this study, we examine midlife marital status trajectories and their association with dementia and mild cognitive impairment (MCI) at ages 70 plus using a large population based sample from Norway. Methods: Based on a general population sample linked to population registries (N = 8706), we used multinomial logistic regression to examine the associations between six types of marital trajectories (unmarried, continuously divorced, intermittently divorced, widowed, continuously married, intermittently married) between age 44 and 68 years from national registries and a clinical dementia or a MCI diagnosis after age 70. We estimated relative risk ratios (RRR) and used mediation analyses adjusting for education, number of children, smoking, hypertension, obesity, physical inactivity, diabetes, mental distress, and having no close friends in midlife. Inverse probability weighting and multiple imputations were applied. The population attributable fraction was estimated to assess the potential reduction in dementia cases due to marital histories. Results: Overall, 11.6% of the participants were diagnosed with dementia and 35.3% with MCI. Dementia prevalence was lowest among the continuously married (11.2%). Adjusting for confounders, the risk of dementia was higher for the unmarried (RRR = 1.73; 95% CI: 1.24, 2.40), continuously divorced (RRR = 1.66; 95% CI: 1.14, 2.43), and intermittently divorced (RRR = 1.50; 95% CI: 1.09, 2.06) compared to the continuously married. In general, marital trajectory was less associated with MCI than with dementia. In the counterfactual scenario, where all participants had the same risk of receiving a dementia diagnosis as the continuously married group, there would be 6.0% fewer dementia cases. Discussion: Our data confirm that staying married in midlife is associated with a lower risk of dementia and that divorced people account for a substantial share of dementia cases.

Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to investigate whether a 5-year exercise intervention and change in peak oxygen uptake ([Formula: see text]) is associated with cognitive function in older adults. METHODS: Nine hundred and forty-five participants (48% women, mean age at study end 78.2 ± 2.02 years) from the Generation 100 Study were randomized 2:1:1 to a control group, moderate-intensity continuous training or high-intensity interval training twice weekly for 5 years. Peak oxygen uptake was measured using ergospirometry at baseline and after 5 years. Global cognition and mild cognitive impairment (MCI) were assessed with the Montreal Cognitive Assessment scale (MoCA) after 5 years. RESULTS: Compared to the control group, the combined moderate-intensity continuous training plus high-intensity interval training (ExComb) group did not have significantly different cognitive scores (beta value 0.26, 95% confidence interval [CI] - 0.17, 0.69) or odds of MCI (odds ratio 0.86, 95% CI 0.66, 1.13). Men in the ExComb group had 0.80 points higher MoCA (95% CI 0.21, 1.40) and 32% lower odds of MCI compared with male controls (95% CI 0.47, 0.99), with no such findings in women. In the total sample, each 1 metabolic equivalent of task increase in [Formula: see text] corresponded to 0.46 points higher MoCA (95% CI 0.25, 0.67) and 27% lower odds of MCI (95% CI 0.63, 0.85). Compared to [Formula: see text] stable, participants whose [Formula: see text] increased did not have significantly different cognitive scores (beta value 0.24, CI - 0.68, 1.15) or odds of MCI (odds ratio 0.70, 95% CI 0.36, 1.34), whereas participants whose [Formula: see text] decreased had 0.64 points lower MoCA (95% CI - 1.15, - 0.14) and 35% higher odds of MCI (95% CI 0.98, 1.87). CONCLUSIONS: Overall, exercise was not significantly associated with cognition among older adults. However, maintaining or increasing [Formula: see text] appeared to benefit cognition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

Long-term changes in body weight and physical activity in relation to all-cause and cardiovascular mortality: the HUNT study.

BACKGROUND: Most previous studies have relied on single measurements of body weight and physical activity and have not considered the interplay between long-term changes in body weight and physical activity in relation to mortality. The aim of the current study was therefore to examine the joint effect of changes in body weight and leisure-time physical activity over a period of ~ 10 years on all-cause and cardiovascular mortality. METHODS: The study population comprised 34,257 individuals who participated in the first (1984-86) and second (1995-97) waves of the HUNT Study, and were followed up through the Norwegian Cause of Death Registry until December 31st, 2013. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) of death associated with changes in body weight and leisure-time physical activity. RESULTS: Compared to the reference group with stable weight who were long-term physically active, people who gained ≥5% of their weight had a HR for all-cause mortality of 1.54 (95% CI: 1.28-1.85) if they were long-term physically inactive; a HR of 1.23 (1.09-1.40) if they became physically active, and a HR of 1.00 (95% CI 0.94-1.06) if they were long-term physically active. The corresponding HRs for cardiovascular mortality were 1.57 (95% CI 1.17-2.12), 1.28 (95% CI 1.04-1.58) and 1.06 (95% CI 0.96-1.16), respectively. Long-term physical inactivity was associated with increased all-cause (HR 1.29; 95% CI 1.08-1.53) and cardiovascular (HR 1.37; 95% CI 1.05-1.79) mortality among those who were weight stable. CONCLUSIONS: The risk of all-cause and cardiovascular mortality is particularly evident among people who gain weight while remaining inactive during a ~ 10 year period. However, participants who remained physically active had the lowest risk of premature mortality, regardless of maintenance or increase in weight. These findings suggest that there is an interplay between long-term changes in body weight and physical activity that should receive particular attention in the prevention of premature mortality.

Associations of Changes in Cardiorespiratory Fitness and Symptoms of Anxiety and Depression With Brain Volumes: The HUNT Study.

Objective: We investigated the independent and joint associations of changes in estimated cardiorespiratory fitness (eCRF) and symptoms of anxiety and depression with brain volumes in individuals from the general population. Method: 751 participants (52% women, aged 50-67 years) from the Nord-Trøndelag Health Study (HUNT) MRI cohort were included. eCRF obtained from a non-exercise algorithm and symptoms of anxiety and depression were assessed twice; at HUNT2 (1995-97) and HUNT3 (2006-08). Brain MRI was performed shortly after HUNT3. Brain parenchymal fraction (BPF), bilateral hippocampal and total cortical volume were extracted from brain MRI obtained at 1.5T, using FreeSurfer and Statistical Parametric Mapping. Results: Multiple regression revealed that participants whose eCRF increased had larger BPF (ß = 0.09, 95% CI 0.02, 0.16) and larger hippocampal volume (ß = 0.09, 95% CI 0.03, 0.16) compared to participants whose eCRF remained low. Participants whose eCRF remained high had larger BPF (ß = 0.15, 95% CI 0.07, 0.22) and larger cortical volume (ß = 0.05, 95% CI 0.01, 0.09). Participants whose anxiety symptoms worsened had smaller BPF (ß = -0.09, 95% CI -0.15, -0.02) and cortical volume (ß = -0.05, -0.08, -0.01) than participants whose anxiety symptoms remained low. Each ml/kg/min increase in eCRF was associated with larger cortical volume among individuals with worsening of anxiety symptoms (ß = 0.13, 95% CI 0.001, 0.27), and larger BPF among individuals whose depressive symptoms improved (ß = 0.28, 95% CI 0.02, 0.53). Conclusion: Promoting exercise intended to improve eCRF may be an important public health initiative aimed at maintaining brain health among middle-aged individuals with and without changing psychological symptoms.

Midlife Physical Activity, Psychological Distress, and Dementia Risk: The HUNT Study.

BACKGROUND: Physical activity (PA) is associated with a decreased dementia risk, whereas psychological distress (distress) is linked to an increased dementia risk. OBJECTIVE: We investigated independent and joint associations of midlife moderate-to-vigorous PA (MVPA) and distress with incident dementia. METHODS: Our study comprised 28,916 participants aged 30-60 years from the Nord-Trøndelag Health Study (HUNT1, 1984-1986). Data on MVPA and distress from HUNT1 was linked to the Health and Memory Study in Nord-Trøndelag for dementia case identification. Participants were followed from 1995 until 2011. We used adjusted Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: In fully adjusted analyses, MVPA was associated with a reduced dementia risk (HR 0.81, 95% CI 0.62-1.06), compared to no MVPA. Distress was associated with an increased dementia risk (HR 1.30, 95% CI 0.99-1.70). Compared to distressed participants not taking part in MVPA, non-distressed no-MVPA participants had a reduced dementia risk (HR 0.72, 95% CI 0.54-0.96). The same applied to distressed MVPA participants (HR 0.50, 95% CI 0.22-1.14), and non-distressed MVPA participants (HR 0.63, 95% CI 0.44-0.90). Our results indicated an additive interaction between MVPA and distress on dementia risk. CONCLUSION: Our results suggest that midlife MVPA reduces risk of incident dementia among both distressed and non-distressed individuals.

Leisure-Time Physical Activity Is Associated With Reduced Risk of Dementia-Related Mortality in Adults With and Without Psychological Distress: The Cohort of Norway.

Background: Leisure-time physical activity (PA) has been proposed as a protective factor against dementia, whereas psychological distress is associated with an increased risk of dementia. We investigated the associations of leisure-time PA and psychological distress with dementia-related mortality, and whether the association between leisure-time PA and dementia-related mortality differs according to level of psychological distress. Methods: 36,945 individuals from the Cohort of Norway aged 50-74 years at baseline (1994-2002) were included and followed up until January 1st 2015. Leisure-time PA and psychological distress were assessed through questionnaires, whereas dementia-related mortality was obtained through the Norwegian Cause of Death Registry. Adjusted Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Results: Compared to inactivity, leisure-time PA was associated with a decreased risk of dementia-related mortality; low intensity leisure-time PA (HR = 0.73, 95% CI 0.59-0.89); high intensity leisure-time PA (HR = 0.61, 95%CI 0.49-0.77). A statistically significant difference in dementia-related mortality risk was observed between low and high intensity leisure-time PA (p < 0.05). Psychological distress was associated with an increased risk of dementia-related mortality (HR = 1.45, 95% CI 1.16-1.81). Among non-distressed, leisure-time PA was associated with a decreased dementia-related mortality risk; low intensity leisure-time PA (HR = 0.77, 95% CI 0.61-0.97); high intensity leisure-time PA (HR = 0.65, 95% CI 0.51-0.84). The same applied for those with psychological distress; low intensity leisure-time PA (HR = 0.57, 95% CI 0.35-0.94); high intensity leisure-time PA (HR = 0.42, 95% CI 0.22-0.82). The interaction between leisure-time PA and psychological distress on dementia-related mortality was not statistically significant (p = 0.38). Conclusions: Participating in leisure-time PA was associated with a reduced risk of dementia-related mortality, whereas psychological distress was associated with an increased risk of dementia-related mortality. Leisure-time PA appears to be equally strongly related with dementia-related mortality among those with and without psychological distress, underlining the importance of leisure-time PA for various groups of middle-aged and older adults.