Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition.

Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (-4.6 pg/mL, 95% CI: -7.84, -1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.

Subjective sleep quality and daytime sleepiness in late midlife and their association with age-related changes in cognition.

UNLABELLED: In an increasingly aged population, sleep disturbances and neurodegenerative disorders have become a major public health concern. Poor sleep quality and cognitive changes are complex health problems in aging populations that are likely to be associated with increased frailty, morbidity, and mortality, and to be potential risk factors for further cognitive impairment. We aimed to evaluate whether sleep quality and excessive daytime sleepiness may be considered as early predictors of cognitive impairment. STUDY OBJECTIVES: The objective of this study was to examine whether subjective sleep quality and daytime sleepiness are associated with cognition in middle-aged males. PARTICIPANTS: A total of 189 healthy males born in 1953 were considered as participants for the study. Based on previous cognitive assessments, the participants were selected for the study as cognitively improved (N = 97) or cognitively impaired (N = 92). METHODS: The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale measured subjective sleep quality and daytime sleepiness, respectively. Depressive symptoms were determined using Beck's Depression Inventory (BDI-II). A neuropsychological battery was administered to confirm group differences in cognitive functioning at the time when sleep data were collected. RESULTS: Compared with cognitively improved males, the cognitively impaired group reported significantly lower subjective sleep quality (5.40 ± 3.81 vs. 4.39 ± 2.40, p = 0.03). Forty-one percent of the sample exhibited poor sleep quality and 15% experienced excessive daytime sleepiness. There were few correlations between sleep parameters and cognitive test performance in the combined sample. CONCLUSION: Self-reported poor sleep quality was related to cognitive changes, whereas daytime sleepiness was not related. Our results suggest that sleep quality may be an early marker of cognitive decline in midlife.

Does physical exposure throughout working life influence chair-rise performance in midlife? A retrospective cohort study of associations between work and physical function in Denmark.

OBJECTIVES: Our aim was to study associations between physical exposures throughout working life and physical function measured as chair-rise performance in midlife. METHODS: The Copenhagen Aging and Midlife Biobank (CAMB) provided data about employment and measures of physical function. Individual job histories were assigned exposures from a job exposure matrix. Exposures were standardised to ton-years (lifting 1000 kg each day in 1 year), stand-years (standing/walking for 6 h each day in 1 year) and kneel-years (kneeling for 1 h each day in 1 year). The associations between exposure-years and chair-rise performance (number of chair-rises in 30 s) were analysed in multivariate linear and non-linear regression models adjusted for covariates. RESULTS: Mean age among the 5095 participants was 59 years in both genders, and, on average, men achieved 21.58 (SD=5.60) and women 20.38 (SD=5.33) chair-rises in 30 s. Physical exposures were associated with poorer chair-rise performance in both men and women, however, only associations between lifting and standing/walking and chair-rise remained statistically significant among men in the final model. Spline regression analyses showed non-linear associations and confirmed the findings. CONCLUSIONS: Higher physical exposure throughout working life is associated with slightly poorer chair-rise performance. The associations between exposure and outcome were non-linear.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

BACKGROUND AND OBJECTIVES: Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. DESIGN: Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. METHODS: Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. RESULTS: Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. CONCLUSIONS: The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

Leisure activity associated with cognitive ability level, but not cognitive change.

Although activity participation is promoted as cognitively protective, critical questions of causality remain. In a cohort followed every 5 years from age 75 to 85 years, potential reciprocal associations between level and change in leisure activity participation and level and change in cognitive abilities were examined. Participants in the Glostrup 1914 Cohort, a longitudinal study of aging, completed standardized cognitive ability tests and reported their leisure activity participation (11 activities defined a leisure activity score) at ages 75, 80, and 85. Higher leisure activity was associated with higher cognitive ability (significant correlations ranged from 0.15 to 0.31, p < 0.05). Between ages 75 and 85, participation in leisure activities and cognitive ability declined significantly. Growth curve models, which provided latent variables for level of and 10-year change in both leisure activity and cognitive ability, confirmed the positive association between levels of leisure activity and cognitive ability (path coefficient = 0.36, p < 0.001); however, neither leisure activity level nor change in leisure activity were associated with cognitive change. Although a positive association between leisure activity and cognitive ability was reported-the likely precedents of this are discussed-there was no evidence that a higher level or maintenance of leisure activity was protective against cognitive decline across a 10-year follow-up.

Assessing fatigue in late-midlife: increased scrutiny of the Multiple Fatigue Inventory-20 for community-dwelling subjects.

Previous methods examining the Multiple Fatigue Inventory-20 (MFI-20) fatigue questionnaire have been limited to classical test theory, for example, factor analytic approaches. We employed modern test theory to further strengthen the construct validity of the MFI-20 fatigue in a sample of healthy late-midlife subjects. Five subdimensions of perceived fatigue were examined in n = 7,233 subjects: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Fatigue burden was compared across age groups (aged 48-52 vs. 57-63) and gender. Mokken item response theory was used to investigate dimensionality, monotonicity, and invariant item ordering (IIO). In both age groups, as well as by gender, the Motivation domain presented with weak scalability, suggesting that caution be exercised when interpreting sum scores. For all groupings, the strongest scaling properties were observed in the General Fatigue domain. However, the General Fatigue domain did not meet the property of IIO. Two domains (for all groupings) did meet the minimum criteria for the property of IIO: Physical Fatigue and Activity. Introducing model parameters for items served to enhance the interpretive power of the MFI-20, allowing for the identification of the most optimal scales. Poorly performing items were more easily identified, and person ability was assessed more accurately.

Self-reported fatigue and physical function in late mid-life.

OBJECTIVE: To determine the association between the 5 subscales of the Multidimensional Fatigue Inventory (MFI-20) and physical function in late mid-life. DESIGN: Cross-sectional study. SUBJECTS: A population-based sample of adults who participated in the Copenhagen Aging and Midlife Biobank population cohort (n = 4,964; age 49-63 years). METHODS: Self-reported fatigue was measured using the MFI-20 comprising: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Handgrip strength and chair rise tests were used as measures of physical function. Multiple logistic regression analyses were used to determine the associations between handgrip strength and the chair rise test with the MFI-20 subscales, adjusted for potential confounders. RESULTS: After adjustments for potential confounders, handgrip strength was associated with physical fatigue (adjusted odds ratio (OR) 0.75 (95% confidence interval (CI) 0.66-0.86); p ≤ 0.001) and reduced motivation (adjusted OR 0.85 (95% CI 0.75-0.96); p ≤ 0.05), but not with the other subscales. After these adjustments, the chair rise test was associated with physical fatigue (adjusted OR 0.61 (0.53-0.69); p ≤ 0.001), general fatigue (adjusted OR 0.72 (0.62-0.84); p ≤ 0.001), reduced activity (adjusted OR 0.79 (0.70-0.90); p ≤ 0.001) and reduced motivation (adjusted OR 0.84 (0.74-0.95); p ≤ 0.01), but not with mental fatigue. Subgroup analyses for sex did not show statistically significant different associations between physical function and fatigue. CONCLUSION: The present study supports the physiological basis of 4 subscales of the MFI-20. The association between fatigue and function was independent of gender.

Fatigue and depressive symptoms in older people.

Fatigue is considered an important indicator of aging-related declines in health and functional abilities. Previous studies have indicated strong associations between fatigue and depressive symptoms among younger populations and in patient groups with specific diseases. However, it is not known how different measures of fatigue are associated with depressive symptoms among general older populations. The purpose of this study is to describe the prevalence of depressive symptoms among community-dwelling older adults reporting mobility-related or general feelings fatigue. The study population consisted of 75-year-old community-living individuals (n = 561). Both, mobility-related and general fatigue, were associated in a stepwise relationship with depressive symptoms: a higher level of fatigue was related to higher level of depressive symptoms. Especially major general fatigue was strongly associated with high level of depressive symptoms. It is important for professionals of the field to be aware of the associations between different measures of fatigue and depressive symptoms.

Association of leukocyte telomere length with fatigue in nondisabled older adults.

Introduction. Fatigue is often present in older adults with no identified underlying cause. The accruing burden of oxidative stress and inflammation might be underlying factors of fatigue. We therefore hypothesized that leukocyte telomere length (LTL) is relatively short in older adults who experience fatigue. Materials and Methods. We assessed 439 older nondisabled Danish twins. LTL was measured using Southern blots of terminal restriction fragments. Fatigue was measured by the Mob-T Scale based on questions on whether the respondents felt fatigued after performing six mobility items. Results. LTL was significantly associated with fatigue (P = 0.023), showing an increase of 0.038 kb/fatigue score unit. Aging-related diseases and mental health did not explain the association, while lifestyle factors slightly attenuated the estimates. Conclusion. Our results support an association between LTL and fatigue. Further studies are required to confirm this finding and the link of LTL with oxidative stress/inflammation over the life course.

Psychosocial factors at work and the development of mobility limitations among adults in Denmark.

AIM: Psychosocial factors in the working environment have been shown to be associated with mobility limitations, but this has not yet been confirmed in a Danish population. We aimed to examine how psychosocial factors at work are related to developing mobility limitations in Denmark. METHODS: This study is based on data from 2952 middle-aged men and women without mobility limitations in 2000. RESULTS: We found increased risk of incident mobility limitations during 6-year follow up among men who often perceived high work pace (OR 5.45, 95% CI 1.21-24.52) vs. never, who only sometimes or/never perceived the work to be meaningful (OR 6.54, 95% CI 1.55-27.55) vs. always, and who sometimes perceived high emotional demands at work (OR 7.85, 95% CI 1.78-34.65) vs. never. Among women, lower risk of incident mobility limitations was observed among those who in 2000 perceived high work pace sometimes (OR 0.46, 95% CI 0.24-0.87) or often (OR 0.43, 95% CI 0.22-0.85) vs. never in 2000. Also, women who always or often experienced high emotional demands had an increased risk. CONCLUSIONS: The most important finding was that high work pace was strongly associated with increased risk of mobility limitations among men, but associated with lower risk of mobility limitations among women. This knowledge may be used to better target interventions among men and women in midlife from physical deterioration later in life.

Personality in late midlife: associations with demographic factors and cognitive ability.

OBJECTIVES: To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits and cognitive ability in late midlife; and to evaluate how these associations are influenced by demographic factors. METHODS: The study sample comprised 5,397 late midlife participants from three cohorts who had completed the NEO Five-Factor Inventory (NEO-FFI) and a measure of cognitive ability. RESULTS: Associations were demonstrated between the five NEO-FFI personality traits, and all included demographic factors. Cognitive ability and years of education correlated with several NEO-FFI personality traits in analyses adjusting for demographic variables. Cohort differences were observed for Extraversion and Openness. DISCUSSION: Robust sex, educational, and social class differences in personality may contribute to late midlife social gradients in health and early aging. Demographic factors did not fully explain correlations between personality and cognitive ability or cohort differences in personality.

The relationship between cognitive ability and demographic factors in late midlife.

OBJECTIVE: The aim of the article is to analyze associations between sex, age, education, and social class and cognitive ability in late midlife and to evaluate differences in cognitive ability among the three Copenhagen Aging and Midlife Biobank (CAMB) cohorts. METHOD: The sample comprised 5,417 CAMB participants from three cohorts with scores on the Intelligenz-Struktur-Test 2000 R (I-S-T 2000 R). RESULTS: Independent associations of cognitive ability with age, sex, education, and occupational social class were observed. Particularly, strong associations with cognitive ability were obtained for school education, and consistent sex differences were observed with higher cognitive ability in men. Differences in cognitive ability among the three cohorts were small and primarily reflected demographic differences. DISCUSSION: Late-midlife cognitive ability is associated with a number of demographic factors, and demographic differences may contribute to individual differences in health and early aging. In analyses of cognitive ability, the three CAMB cohorts can be combined provided the relevant demographic variables are included as covariates.

Smoking and drinking as risk indicators for tooth loss in middle-aged Danes.

OBJECTIVES: To investigate tobacco and alcohol consumption as risk indicators for missing teeth in late middle-aged Danes. METHOD: In all, 1,517 Copenhagen Aging and Midlife Biobank (CAMB) participants received a clinical oral examination that included number of teeth. Information on smoking, drinking, and various covariates was obtained using self-administered, structured questionnaires. Descriptive statistics and logistic regression (dependent variable: 6+ vs. <6 missing teeth) were used to investigate smoking and drinking in relation to missing teeth. RESULTS: Current smokers, persons who currently or previously smoked >15 tobacco units/day, and persons who had smoked for 27+ years had elevated mean scores of missing teeth and associated odds ratios (OR) compared with never smokers. Relative to nondrinkers, alcohol consumption was associated with reduced odds of missing 6+ teeth. DISCUSSION: Our findings suggest that smoking is positively associated, while alcoholic beverage consumption is inversely related to tooth loss in middle-aged Danes.

Social class differences in physical functions in middle-aged men and women.

OBJECTIVE: The objective of the present study is to analyze gender differences and social class gradients in physical functions; and to study whether the social class gradients in physical functions in midlife differed between men and women. METHOD: This study used traditionally used physical performance tests and we added several tests of vigorous physical functioning (trunk muscle strength and power and sagittal flexibility). We measured reaction time, one-legged balance, sagittal flexibility, jump height, chair rise ability, trunk muscle- and handgrip strength in 5,412 participants aged 50 to 60 years (68.5% men). RESULTS: We found gender differences and social class gradients for all physical performance tests. We did not find an interaction between social class and gender, indicating that the social gradient in physical functions did not differ between men and women. DISCUSSION: Including measures of vigorous physical functioning may add to the existing knowledge on development of functional limitation and poorer functional health later in life.

Social gradient in allostatic load among Danish men and women in late midlife.

OBJECTIVE: The objective of the present study is to describe the prevalence of allostatic load (AL) among Danish men and women in late midlife, and if there is a social gradient in AL. METHOD: A total of 5,420 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48 to 63 years (68.5% men, 31.5% women) underwent a health examination including standardized measures of height, weight, body fat, and blood pressure in 2009-2011. AL (range 0-14) was established by summing the scores of the poorest quartile for each of 14 biological variables related to the metabolic and immune systems. RESULTS: We found a social gradient in AL in late midlife among men and women living in Denmark. DISCUSSION: AL may be a potential biomarker for early aging in countries with a strong social welfare system. It is important for intervention studies to be aware of this type of biological vulnerability already present in late midlife.

Addressing social inequality in aging by the Danish occupational social class measurement.

OBJECTIVE: To present the Danish Occupational Social Class (DOSC) measurement as a measure of socioeconomic position (SEP) applicable in a late midlife population, and to analyze associations of this measure with three aging-related outcomes in midlife, adjusting for education. METHOD: Systematic coding procedures of the DOSC measurement were applied to 7,084 participants from the Copenhagen Aging and Midlife Biobank (CAMB) survey. We examined the association of this measure of SEP with chronic conditions, self-rated health, and mobility in logistic regression analyses, adjusting for school education in the final analysis. RESULTS: The measure of SEP showed a strong social gradient along the social classes in terms of prevalence of chronic conditions, poor self-rated health, and mobility limitations. Adjusting for school education attenuated the association only to a minor degree. DISCUSSION: The DOSC measure was associated with aging-related outcomes in a midlife Danish population, and is, thus, well suited for future epidemiological research on social inequalities in health and aging.

Content validity and reliability of the Copenhagen social relations questionnaire.

OBJECTIVE: The aim of the present article is to describe the face and content validity as well as reliability of the Copenhagen Social Relations Questionnaire (CSRQ). METHOD: The face and content validity test was based on focus group discussions and individual interviews with 31 informants. Another 94 men and women participated in an 8-day test-retest analysis. RESULTS: Informants generally expressed that the questions and response categories were relevant and easy to understand. Themes on structure of social relations, social support, and negative aspects of social relations emerged clearly from the interviews. Two additional themes not covered by CSRQ on dynamics and reciprocity of social relations were identified. DISCUSSION: CSRQ holds satisfactory face and content validity as well as reliability, and is suitable for measuring structure and function of social relations including the negative aspects among middle-aged individuals.

Subclinical cognitive decline in middle-age is associated with reduced task-induced deactivation of the brain's default mode network.

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging.

Educational intervention and functional decline among older people: the modifying effects of social capital.

AIM: To analyse if social capital modifies the effect of educational intervention of home visitors on mobility disability. Earlier studies have found that educational intervention of home visitors has a positive effect of older peoples' functional decline, but how social capital might modify this effect is still unknown. METHODS: We used the Danish Intervention Study on Preventive Home Visits - a prospective cohort study including 2863 75-year-olds and 1171 80-year-olds in 34 Danish municipalities - to analyse the modifying effect of different aspects of social capital on the effect of educational intervention of home visitors on functional decline. The three measures of social capital (bonding, bridging, and linking) were measured at contextual level. Data was analysed with multivariate linear regression model using generalised estimating equations to account for repeated measurements. RESULTS: We found that 80-year-olds living in municipalities with high bonding (B=0.089, p=0.0279) and high linking (B=0.0929; p=0.0217) had significant better mobility disability in average at 3-year follow up if their municipality had received intervention. CONCLUSIONS: With the unique design of the Danish Intervention Study on Preventive Home Visits and with theory-based measures of social capital that distinguish between three aspects of social capital with focus on older people, this study contributes to the literature about the role of social capital for interventions on mobility disability.