Does moderate to vigorous physical activity mediate the association between depression and physical function in midlife: Evidence from two British birth cohort studies.

BACKGROUND: Mental health and physical health are intrinsically linked, yet the mechanisms are not well understood. We investigated whether moderate-vigorous physical activity (MVPA) mediated the association between depression and physical function (PF) in midlife. METHODS: Individuals from two UK birth cohorts born within one week in 1958 (n = 7278) and 1970 (n = 6097) with data on depression (ages 33/34; Malaise Inventory), MVPA (age 42; self-reported) and PF (ages 50/56; Short Form-36 subscale). Covariates included sex, childhood and adulthood social class, maternal mental health, childhood mood, alcohol consumption, smoking habits, sleep, marital status, BMI and long-standing illness/disability. Linear or multinomial logistic regression models examined associations between depression, MVPA and PF. We used a parametric g-computation mediation analysis approach to estimate percent differences in PF. RESULTS: Depression was associated with less frequent MVPA and poorer PF. Lower MVPA was associated with worse PF. The direct effect - randomised analogue not operating via MVPA - of depression on PF was -18.8 % (95%CI:--25.8,-11.8) and -15.8 % (20.6,-11.0) in the 1958 and 1970 cohorts, respectively. The indirect effect - operating via MVPA - was -0.5 % (-1.0,-0.03) and -0.2 % (-0.6, 0.3), resulting in a total proportion mediated of 3.1 % (0.1, 6.0) and 0.9 % (-1.6, 3.4). LIMITATIONS: MVPA was self-reported. Intermediate confounders and mediators were measured at the same age, however associations did not change in sensitivity analysis considering age 46 MVPA (1958 cohort). CONCLUSIONS: Although higher MVPA was protective against poor PF, there was only minor evidence that it mediated the association between depression and PF. Further investigation into other potential mediators of pathways from mental to physical health is needed.

Lifetime body mass index and grip strength at age 46 years: the 1970 British Cohort Study.

BACKGROUND: Ongoing rises in obesity prevalence have prompted growing concerns about potential increases in the burden of age-related musculoskeletal conditions including sarcopenia and sarcopenic obesity. This is of particular concern for future generations of older adults who have lived more of their lives in an obesogenic environment than current generations of older adults. We aimed to study longitudinal associations between body mass index (BMI) and grip strength in midlife using data from a large population-based sample, the 1970 British Cohort Study (BCS70). METHODS: BCS70 participants with valid measures of maximum grip strength at age 46 years were included in analyses [3671 males (49%) and 3876 females (51%)]. Using sex-specific linear regression models, we examined associations of (i) BMI at ages 10, 16, 30, and 46 years; (ii) body fat percentage (BF%) and waist-hip ratio at age 46 years; (iii) BMI gains between 10-16, 16-30, and 30-46; and (iv) age at onset of obesity, with grip strength. RESULTS: At age 46 years, mean (standard deviation) grip strength was 48.10 kg (8.98) in males and 29.61 kg (5.81) in females. Higher BMI at all ages was associated with stronger grip, and the scale of associations was greater in males than females from age 16 onwards (Psex interactions  < 0.01). For example, in fully adjusted models, a 1 standard deviation increase in BMI at age 16 was associated with mean differences in grip strength at age 46 years of 1.41 kg (95% confidence interval: 1.07, 1.75) in males and 0.72 kg (0.53, 0.91) in females. Higher BF% at age 46 was also associated with stronger grip in both sexes. Greater gains in BMI between ages 10 and 16 were associated with stronger grip in both sexes, but subsequent gains in BMI were only associated with stronger grip in males. Associations of greater length of exposure to obesity and stronger grip were also more consistent among males than females. For example, in fully adjusted models, mean grip strength at age 46 years of males and females who had been obese since age 10 or 16 years was 4.39 kg (1.85, 6.93) and 1.25 kg (-0.18, 2.69) higher than males and females who had never been obese, respectively. CONCLUSIONS: Higher BMI from childhood onwards is associated with stronger grip at age 46 years. This suggests that, at this age, anabolic effects of fat on muscle are outweighing the catabolic effects thought to lead to the manifestation of sarcopenic obesity later in life, especially among men. Midlife may be an optimal time to intervene to prevent sarcopenic obesity.

Depressive symptoms during early adulthood and the development of physical multimorbidity in the UK: an observational cohort study.

BACKGROUND: An understanding of whether early-life depression is associated with physical multimorbidity could be instrumental for the development of preventive measures and the integrated management of depression. We therefore aimed to map out the cumulative incidence of physical multimorbidity over adulthood, and to determine the association between the presence of depressive symptoms during early adulthood and the development of physical multimorbidity in middle age. METHODS: In this observational cohort study, we used pooled data from the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS). Cohort waves were pooled in each decade of adult life available (when cohort members were aged 26 years in the BCS and 23 years in the NCDS [baseline]; 34 years in the BCS and 33 years in the NCDS [age 34 BCS/33 NCDS]; 42 years in the BCS and NCDS [age 42 BCS/NCDS]; and 46 years in the BCS and 50 years in the NCDS [age 46 BCS/50 NCDS]). We included participants who had completed the nine-item Malaise Inventory at baseline, and did not have a history of physical multimorbidity, any physical multimorbidity at baseline, or the presence of depressive symptoms before the development of physical multimorbidity. The presence of depressive symptoms was determined using the nine-item Malaise Inventory (cutoff score ≥4). Physical multimorbidity was defined as having at least two measures of any of the following ten self-reported groups of long-term conditions: asthma or bronchitis; backache; bladder or kidney conditions; cancer; cardiovascular conditions; convulsions or epilepsy; diabetes; hearing conditions; migraine; and stomach, bowel, or gall conditions. Cumulative incidence (with 95% CI) of physical multimorbidity was calculated for each decade considered after baseline, with physical multimorbidity being assessed as both a dichotomous and categorical variable. The association between depressive symptoms and the development of physical multimorbidity was assessed using adjusted relative risk ratios (with 95% CIs). FINDINGS: Analyses included 15 845 participants, of whom 4001 (25·25%; 95% CI 24·57-25·93) had depressive symptoms at baseline and 11 844 (74·75%; 74·07-75·42) did not. The cumulative incidence of physical multimorbidity (dichotomous) ranged over the study period from 2263 (18·44%; 95% CI 17·75-18·14) of 12 273 participants at age 34 BCS/33 NCDS, to 4496 (42·90%; 41·95-43·85) of 10 481 participants at age 46 BCS/50 NCDS, and was consistently higher in participants with depressive symptoms at baseline. The adjusted relative risk of physical multimorbidity was higher in participants with depressive symptoms than in those without and remained stable over the study period (adjusted relative rate ratio 1·67, 95% CI 1·50-1·87, at age 34 BCS/33 NCDS; 1·63, 1·48-1·79, at age 42 BCS/NCDS; and 1·58, 1·43-1·73, at age 46 BCS/50 NCDS). INTERPRETATION: The presence of depressive symptoms during early adulthood is associated with an increased risk of the development of physical multimorbidity in middle age. Although further research about the drivers of this relationship is needed, these results could help to enhance the integrated management of individuals with depressive symptoms and the development of preventive strategies to reduce the effect and burden of physical multimorbidity. FUNDING: UK Medical Research Council and Guy's Charity.

Child maltreatment, early life socioeconomic disadvantage and all-cause mortality in mid-adulthood: findings from a prospective British birth cohort.

OBJECTIVES: Early-life adversities (ELAs) such as child maltreatment (neglect and abuse) and socioeconomic disadvantage have been associated with adult mortality. However, evidence is sparse for specific types of ELA. We aimed to establish whether specific ELAs (ie, different types of child maltreatment and socioeconomic disadvantage) were associated independently with all-cause mortality in mid-adulthood and to examine potential intermediary pathways. DESIGN: Prospective cohort study. SETTING: 1958 British birth cohort: a longitudinal, population-based sample of individuals born in Great Britain during a single week in March 1958. PARTICIPANTS: 9310 males and females with data on child maltreatment and mortality (44/45-58 years). OUTCOME MEASURES: Mortality follow-up from 2002/2003 to 2016 when participants were aged 44/45-58 years. Death was ascertained via the NHS Central Register (N=296) or cohort maintenance activities (N=16). RESULTS: Prevalence of ELAs ranged from 1.6% (sexual abuse) to 11% (psychological abuse). Several, but not all, ELAs were associated with increased risk of premature death, independent of covariates and other adversities; adjusted HRs were 2.64 (95% CI 1.52 to 4.59) for sexual abuse, 1.93 (95% CI 1.45 to 2.58) for socioeconomic disadvantage, 1.73 (95% CI 1.11 to 2.71) for physical abuse and 1.43 (95% CI 1.03 to 1.98) for neglect. After adjustment for covariates and other adversities, no associations with mortality were observed for psychological and witnessing abuse. Regarding potential intermediaries (including adult socioeconomic factors, behaviours, adiposity, mental health and cardiometabolic markers), most associations attenuated after accounting for adult health behaviours (particularly smoking). In addition, early-life socioeconomic disadvantage and neglect associations attenuated after accounting for adult socioeconomic factors. The association for sexual abuse and premature mortality was largely unaffected by potential intermediaries. CONCLUSIONS: Associations with premature mortality varied by type of ELA: associations for sexual and physical abuse, neglect and socioeconomic disadvantage were independent of each other. Different types of ELAs could influence premature mortality via different pathways; this requires further research.

An overview of child maltreatment (neglect and abuse) associations with developmental trajectories and long-term outcomes in the 1958 British birth cohort.

Childhood maltreatment types (neglect and psychological, physical, or sexual abuse) are associated with many poor outcomes in adulthood. Yet, research mainly focuses on the cumulative adversity burden rather than specificities and commonalities of associations with adult outcomes and intervening pathways. To build understanding of life-course pathways to a range of outcomes, this overview summarises evidence from several original research studies using the 1958 British Birth Cohort on specific maltreatment types, child development trajectories, adult intermediaries and outcomes. About one-in-five participants were identified as neglected or abused in childhood (~10% were identified for neglect, 10% for psychological abuse, 6% for physical abuse and 1.4% for sexual abuse). Neglect was associated with key dimensions of development, for example, slower height growth, delayed maturation, faster BMI gain, and poorer emotional and cognitive development. Associated adulthood outcomes included harmful behaviours (notably smoking), poorer physical health (e.g. shorter height, excess BMI, poorer blood lipids and glucose, poor-rated health and physical functioning), worse mental health, lower socioeconomic circumstances (e.g. poorer living conditions) and elevated mortality in mid-adulthood. Childhood abuse associations were less widespread and were often only for specific types: most types were unrelated to childhood height and cognitive abilities, but all types were associated with poorer child emotional development, adult mental health, smoking, blood lipids and self-rated health. Additionally, physical abuse was associated with faster BMI gain, higher adult BMI, blood glucose, inflammation and mortality in mid-adulthood; sexual abuse with faster BMI gain, higher adult BMI, poor physical functioning at 50y and higher mortality in mid-adulthood. Adult health measures associated with neglect and abuse are key predictors of serious disease, disability and death. Therefore, neglect and abuse associations with these measures represent an important burden for individuals and society.

Cardiovascular Health and Stroke in Older British Men: Prospective Findings From the British Regional Heart Study.

BACKGROUND AND PURPOSE: Research exploring the utility of cardiovascular health (CVH) and its Life's Simple 7 (LS7) components (body mass index, blood pressure [BP], glucose, cholesterol, physical activity, smoking, and diet) for prevention of stroke in older adults is limited. In the British Regional Heart Study, we explored (1) prospective associations of LS7 metrics and composite CVH scores with, and their impact on, stroke in middle and older age; and (2) if change in CVH was associated with subsequent stroke. METHODS: Men without cardiovascular disease were followed from baseline recruitment (1978-1980), and again from re-examination 20 years later, for stroke over a median period of 20 years and 16 years, respectively. LS7 were measured at each time point except baseline diet. Cox models estimated hazard ratios (95% CI) of stroke for (1) ideal and intermediate versus poor levels of LS7; (2) composite CVH scores; and (3) 4 CVH trajectory groups (low-low, low-high, high-low, high-high) derived by dichotomising CVH scores from each time point across the median value. Population attributable fractions measured impact of LS7. RESULTS: At baseline (n=7274, mean age 50 years), healthier levels of BP, physical activity, and smoking were associated with reduced stroke risk. At 20-year follow-up (n=3798, mean age 69 years) only BP displayed an association. Hazard ratios for intermediate and ideal (versus poor) levels of BP 0.65 (0.52-0.81) and 0.40 (0.24-0.65) at baseline; and 0.84 (0.67-1.05) and 0.57 (0.36-0.90) at 20-year follow-up. With reference to low-low trajectory, the low-high trajectory was associated with 40% reduced risk, hazard ratio 0.60 (0.44-0.83). Associations of CVH scores weakened, and population attributable fractions of LS7 reduced, from middle to old age; population attributable fraction of nonideal BP from 53% to 39%. CONCLUSIONS: Except for BP, CVH is weakly associated with stroke at older ages. Prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors.

Childhood maltreatment and biomarkers for cardiometabolic disease in mid-adulthood in a prospective British birth cohort: associations and potential explanations.

OBJECTIVES: Research on associations between childhood maltreatment and adult cardiometabolic disease risk is sparse. We aimed to investigate associations between different forms of child maltreatment and mid-adult cardiometabolic markers and whether potential intermediaries could account for the associations observed. SETTING: 1958 British birth cohort. PARTICIPANTS: Approximately 9000 cohort members with data on cardiometabolic markers. OUTCOMES: Adult (45y) cardiometabolic markers (blood pressure, lipids and glycated haemoglobin [HbA1c]). RESULTS: Seventeen per cent of participants were identified as neglected; 6.1%, 1.6% and 10.0% were identified as experiencing physical, sexual and psychological abuse, respectively. Childhood neglect and physical abuse were associated with high body mass index (BMI) and large waist circumference when adjusting for early-life covariates. For neglect, the adjusted odds ratio (AOR) was 1.16 (95% CI: 1.02 to 1.32) and 1.15 (1.02 to 1.30) for general and central obesity, respectively, and for physical abuse, the respective AOR was 1.36 (1.13 to 1.64) and 1.38 (1.16 to 1.65). Neglect was also associated with raised triglycerides by 3.9 (0.3 to 7.5)% and HbA1c by 1.2 (0.4 to 2.0)%, and among females, lower high-density lipoprotein cholesterol (HDL-c) by 0.05 (0.01 to 0.08)mmol/L after adjustment. For physical abuse, the AOR was 1.25 (1.00 to 1.56) for high low-density lipoprotein cholesterol, HbA1c was raised by 2.5 (0.7 to 4.3)% (in males) and HDL-c was lower by 0.06 (0.01 to 0.12)mmol/L (in females). Associations for sexual abuse were similar to those for physical abuse but 95% CIs were wide. For psychological abuse, the AOR for elevated triglycerides was 1.21 (1.02 to 1.44) and HDL-c was lower by 0.04 (0.01 to 0.07)mmol/L. Maltreatments were not associated with raised blood pressure. In analyses of potential intermediary factors, several associations attenuated after adjustment for adult lifestyles (mainly smoking and alcohol consumption rather than physical activity) and child-to-adult BMI. CONCLUSIONS: Childhood maltreatments, particularly neglect and physical abuse, were associated with greater adiposity and poorer lipid and HbA1c profiles decades later in adulthood. Associations were modest but independent of early-life factors linked to these outcomes. Findings implicate adult lifestyles as an important intermediary between child maltreatment and outcomes.

Understanding associations of early-life adversities with mid-life inflammatory profiles: Evidence from the UK and USA.

OBJECTIVES: In two cohorts, we aimed to establish associations between early-life adversities and adult inflammation, and whether adult (a) adiposity or (b) socioeconomic disadvantage are key intermediaries. METHODS: In both cohorts (N = 7661, 1958 British birth cohort; N = 1255, MIDUS), information was used on adult inflammatory markers (C-reactive protein (CRP), fibrinogen and (MIDUS only) interleukin-6 (IL-6)), adiposity and socioeconomic disadvantage, and early-life adversities (neglect, emotional neglect, physical, psychological, sexual abuse and childhood disadvantage). RESULTS: Early-life adversities varied from 1.6% (sexual abuse, 1958 cohort) to 14.3% (socioeconomic disadvantage, MIDUS). Across the two cohorts, associations were consistent for physical abuse, e.g. 16.3%(3.01,29.7) and 17.0%(-16.4,50.3) higher CRP in the 1958 cohort and MIDUS respectively. Associations attenuated after accounting for adult adiposity, e.g. physical abuse (1958 cohort) and sexual abuse (MIDUS, non-white participants) associations were abolished. Some associations attenuated after adjustment for adult socioeconomic disadvantage; e.g. 1958 cohort neglect-CRP associations reduced from 23.2%(13.7,32.6) to 17.7%(8.18,27.2). Across the cohorts, no associations were found for psychological abuse or emotional neglect; associations for childhood socioeconomic disadvantage were inconsistent. CONCLUSIONS: Specific early-life adversities are associated with adult inflammation; adiposity is a likely intermediary factor. Weight reduction and obesity prevention may offset pro-inflammatory related adult disease among those who experienced early-life adversities.

Change in health and social factors in mid-adulthood and corresponding changes in leisure-time physical inactivity in a prospective cohort.

BACKGROUND: To identify whether changes in adult health and social factors are associated with simultaneous changes in inactivity. METHODS: Health, social factors and leisure-time inactivity (activity frequency < 1/week) were self-reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline (33y) health and social factors and also patterns of change in factors 33y-to-50y were related to inactivity 33y-to-50y (never inactive, persistently inactive, deteriorating to inactivity, or improving from inactivity) using multinomial logistic regression. RESULTS: Approximately 31% were inactive at 33y and 50y; 35% changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from inactivity). Baseline poor health and obesity were associated with subsequent (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for deteriorating to inactivity (vs never inactive) and improving from inactivity (vs persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively. Adverse changes in health and weight were associated with simultaneous adverse changes in inactivity; e.g. worsening health (vs always good/excellent health) was associated with higher risk of deteriorating to inactivity (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was associated with lower risk of improving from inactivity; there was no association between improving self-efficacy and inactivity change. Downward social mobility was not associated with deteriorating to or improving from inactivity. Changes in depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were not associated with inactivity changes. No associations were observed for employment. CONCLUSIONS: Associated changes in mid-life health factors with deleterious inactivity changes, highlight the importance of maintaining health, weight and self-efficacy across adulthood to deter inactivity.

Combined early and adult life risk factor associations for mid-life obesity in a prospective birth cohort: assessing potential public health impact.

OBJECTIVE: The combined effect of life-course influences on obesity development and thus their potential public health impact is unclear. We evaluated combined associations and predicted probabilities for early and adult life risk factors with central and general obesity in mid-adulthood. SETTING: 1958 British birth cohort. PARTICIPANTS: 4629 males and 4670 females with data on waist circumference. OUTCOME MEASURES: 45 year obesity measured via waist circumference, waist-hip ratio (WHR) and BMI. RESULTS: At 45 years, approximately a third of the population were centrally obese and a quarter were generally obese. Three factors (parental overweight, maternal smoking during pregnancy and adult inactivity) were consistently associated with central and general obesity. Predicted probabilities for waist obesity increased from those with none to all three risk factors (0.15-0.33 in men; 0.19-0.39 in women (ptrend<0.001)), with a similar trend for general obesity. Additional factors (adult smoking, low fibre and heavy alcohol consumption) were associated with WHR obesity, although varying by gender. Prevalence of risk factors was higher in manual than non-manual groups: for example, in men 38% versus 25%, respectively, had ≥2 risk factors for waist and general obesity. CONCLUSIONS: Early-life and adult factors that are amenable to change are highly prevalent and accumulate in association with central and general obesity in mid-adulthood. The increase in probabilities for mid-adult obesity associated with cumulative levels of risk factors suggests the potential for public health impact.

Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

PURPOSE: Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. METHODS: In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. RESULTS: Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. CONCLUSIONS: Adult leisure time inactivity is moderately stable. Early life factors are associated with persistent and deteriorating inactivity over decades in midadulthood but rarely with improvement.

Breast cancer and mammography: knowledge, attitudes, practices and patient satisfaction post-mammography at the San Fernando General Hospital, Trinidad.

Self-administered questionnaires were completed by 314 Trinidadian women, 40 years and older, to ascertain their breast cancer knowledge, attitudes, and practices. Those with higher education had greater knowledge of the benefits of early breast cancer detection (p < .01) and knew that an abnormal mammography result (p = .01) or recall (p < .01) was not necessarily indicative of breast cancer. Inaccurate beliefs particularly that breast compression causes cancer were more likely among those with the least education (p = .04). Obesity and alcohol were identified as risk factors by 29.3% and 12.4%, respectively. Over two-thirds (70%) of mammograms were primarily the doctor's decision. Over 90% of women were satisfied post-mammography, most (94.6%) with plans for future use. Some (15.6%) reported pain and 48.7% reported discomfort, with over 70% of these finding the examination less painful than anticipated. Targeted culturally sensitive awareness campaigns are needed. Clinicians must be sensitized to their importance in recommending mammography. Data on patient satisfaction and pain perception can be publicized to encourage women who are hesitant about mammography.

Localized fibroglandular tissue as a predictor of future tumor location within the breast.

BACKGROUND: Mammographic density (MD) is a strong marker of breast cancer risk, but it is unclear whether tumors arise specifically within dense tissue. METHODS: In 231 British women diagnosed with breast cancer after at least one negative annual screening during a mammographic screening trial, we assessed whether tumor location was related to localized MD 5 years prior to diagnosis. Radiologists identified tumor locations on digitised films. We used a validated algorithm to align serial images from the same woman to locate the corresponding point on the prediagnostic film. A virtual 1 cm square grid was overlaid on prediagnostic films and MD calculated for each square within a woman's breast (mean = 271 squares/film). Conditional logistic regression, matching on a woman's breast, was used to estimate the odds of a tumor arising in a square in relation to its prediagnostic square-specific MD. RESULTS: Median (interquartile range) prediagnostic MD was 98.2% (46.8%-100%) in 1 cm-squares that subsequently contained the tumor and 41.0% (31.5%-53.9%) for the whole breast. The odds of a tumor arising in a 1 cm-square were, respectively, 6.1 (95% CI: 1.9-20.1), 16.6 (5.2-53.2), and 25.5-fold (8.1-80.3) higher for squares in the second, third, and fourth quartiles of prediagnostic MD relative to those in the lowest quartile within that breast (P(trend) < 0.001). The corresponding odds ratios were 2.3 (1.3-4.0), 3.9 (2.3-6.4), and 4.6 (2.8-7.6) if a 3 cm-square grid was used. CONCLUSION: Tumors arise predominantly within the radiodense breast tissue. IMPACT: Localized MD may be used as a predictor of subsequent tumor location within the breast.

Automated registration of diagnostic to prediagnostic x-ray mammograms: evaluation and comparison to radiologists' accuracy.

PURPOSE: To compare and evaluate intensity-based registration methods for computation of serial x-ray mammogram correspondence. METHODS: X-ray mammograms were simulated from MRIs of 20 women using finite element methods for modeling breast compressions and employing a MRI/x-ray appearance change model. The parameter configurations of three registration methods, affine, fluid, and free-form deformation (FFD), were optimized for registering x-ray mammograms on these simulated images. Five mammography film readers independently identified landmarks (tumor, nipple, and usually two other normal features) on pairs of diagnostic and corresponding prediagnostic digitized images from 52 breast cancer cases. Landmarks were independently reidentified by each reader. Target registration errors were calculated to compare the three registration methods using the reader landmarks as a gold standard. Data were analyzed using multilevel methods. RESULTS: Between-reader variability varied with landmark (p < 0.01) and screen (p = 0.03), with between-reader mean distance (mm) in point location on the diagnostic/prediagnostic images of 2.50 (95% CI 1.95, 3.15)/2.84 (2.24, 3.55) for nipples and 4.26 (3.43, 5.24)/4.76 (3.85, 5.84) for tumors. Registration accuracy was sensitive to the type of landmark and the amount of breast density. For dense breasts (> or = 40%), the affine and fluid methods outperformed FFD. For breasts with lower density, the affine registration surpassed both fluid and FFD. Mean accuracy (mm) of the affine registration varied between 3.16 (95% CI 2.56, 3.90) for nipple points in breasts with density 20%-39% and 5.73 (4.80, 6.84) for tumor points in breasts with density < 20%. CONCLUSIONS: Affine registration accuracy was comparable to that between independent film readers. More advanced two-dimensional nonrigid registration algorithms were incapable of increasing the accuracy of image alignment when compared to affine registration.

The spatial distribution of radiodense breast tissue: a longitudinal study.

INTRODUCTION: Mammographic breast density is one of the strongest known markers of susceptibility to breast cancer. To date research into density has relied on a single measure (for example, percent density (PD)) summarising the average level of density for the whole breast, with no consideration of how the radiodense tissue may be distributed. This study aims to investigate the spatial distribution of density within the breast using 493 mammographic images from a sample of 165 premenopausal women (~3 medio-lateral oblique views per woman). METHODS: Each breast image was divided into 48 regions and the PD for the whole breast (overall PD) and for each one of its regions (regional PD) was estimated. The spatial autocorrelation (Moran's I value) of regional PD for each image was calculated to investigate spatial clustering of density, whether the degree of clustering varied between a woman's two breasts and whether it was affected by age and other known density correlates. RESULTS: The median Moran's I value for 165 women was 0.31 (interquartile range: 0.26, 0.37), indicating a clustered pattern. High-density areas tended to cluster in the central regions of the breast, regardless of the level of overall PD, but with considerable between-woman variability in regional PD. The degree of clustering was similar between a woman's two breasts (mean within-woman difference in Moran's I values between left and right breasts = 0.00 (95% confidence interval (CI) = -0.01, 0.01); P = 0.76) and did not change with aging (mean within-woman difference in I values between screens taken on average 8 years apart = 0.01 (95% CI = -0.01, 0.02); P = 0.30). Neither parity nor age at first birth affected the level of spatial autocorrelation of density, but increasing body mass index (BMI) was associated with a decrease in the degree of spatial clustering. CONCLUSIONS: This study is the first to demonstrate that the distribution of radiodense tissue within the breast is spatially autocorrelated, generally with the high-density areas clustering in the central regions of the breast. The degree of clustering was similar within a woman's two breasts and between women, and was little affected by age or reproductive factors although it declined with increasing BMI.

Full-field digital versus screen-film mammography: comparison within the UK breast screening program and systematic review of published data.

PURPOSE: To (a) compare the performance of full-field digital mammography (FFDM), using hard-copy image reading, with that of screen-film mammography (SFM) within a UK screening program (screening once every 3 years) for women aged 50 years or older and (b) conduct a meta-analysis of published findings along with the UK data. MATERIALS AND METHODS: The study complied with the UK National Health Service Central Office for Research Ethics Committee guidelines; informed patient consent was not required, since analysis was carried out retrospectively after data anonymization. Between January 2006 and June 2007, a London population-based screening center performed 8478 FFDM and 31 720 SFM screening examinations, with modality determined by the type of machine available at the screening site. Logistic regression was used to assess whether breast cancer detection rates and recall rates differed between screening modalities. For the meta-analysis, random-effects models were used to combine study-specific estimates, if appropriate. RESULTS: A total of 263 breast cancers were detected. After adjustment for age, ethnicity, area of residence, and type of referral, there was no evidence of differences between FFDM and SFM in terms of detection rates (0.68 [95% confidence interval {CI}: 0.47, 0.89] vs 0.72 [95% CI: 0.58, 0.85], respectively, per 100 screening mammograms; P = .74), recall rates (3.2% [95% CI: 2.8, 3.6] vs 3.4% [95% CI: 3.1, 3.6]; P = .44), positive predictive value (PPV) of an abnormal mammogram, or characteristics of detected tumors. Meta-analysis of data from eight studies showed a slightly higher detection rate for FFDM, particularly at 60 years of age or younger (pooled FFDM-SFM difference: 0.11 [95% CI: 0.04, 0.18] per 100 screening mammograms), but no clear modality differences in recall rates or PPVs. CONCLUSION: Within a routine screening program, FFDM with hard-copy image reading performed as well as SFM in terms of process indicators; the meta-analysis was consistent with FFDM yielding detection rates at least as high as those for SFM.