The Power of Birth Cohorts to Study Risk Factors for Cognitive Impairment

PURPOSE OF REVIEW: Birth cohorts are studies of people the same time; some of which have continuously followed participants across the life course. These are powerful designs for studying predictors of age-related outcomes, especially when information on predictors is collected before these outcomes are known. This article reviews recent findings from these cohorts for the outcomes of cognitive function, cognitive impairment, and risk of dementia, in relation to prior cognitive function, and social and biological predictors. RECENT FINDINGS: Cognitive function and impairment are predicted by a wide range of factors, including childhood cognition, education, occupational status and complexity, and biological factors, including genetic and epigenetic. The particular importance of high and rising blood pressure in midlife is highlighted, with some insight into brain mechanisms involved. Some limitations are noted, including sources of bias in the data. Despite these limitations, birth cohorts have provided valuable insights into factors across the life course associated with cognitive impairment

Subtle Extrapyramidal Signs and Incident Dementia: A Follow-up Analysis

We previously reported [1] that the presence of mild extrapyramidal signs (EPS) significantly predicts Alzheimer's disease (AD) in elderly individuals, independent of age, education, or gender. We now report a confirmation of our data after accrual of more cases and additional follow-up assessments

Pubertal maturation and affective symptoms in adolescence and adulthood: evidence from a prospective birth cohort

The higher prevalence of affective symptoms among women compared to men emerges in adolescence, and it has been associated with pubertal maturation. However, it remains unclear whether pubertal timing has long-term influences on affective symptoms. Using data from the British 1946 birth cohort, we investigated whether pubertal timing was associated with affective symptoms over the life course, distinguishing those with symptoms in adolescence only, symptoms in adulthood only, and symptoms in both adolescence and adulthood. In females, there was no evidence that early pubertal maturation was a risk factor for affective symptoms. However, those with particularly late menarche (≥15 years) showed a lower risk of adult-onset affective symptoms (OR = 0.54, 95% CI: 0.31, 0.95). This effect of late pubertal timing was not explained by a range of socio-behavioural factors. In contrast, in males, late pubertal timing was associated with increased risk of adolescent-onset affective symptoms that tracked into adulthood (OR = 2.10, 95% CI: 1.44, 3.06). This effect was partly explained by low pre-pubertal BMI. Sex-specific effects of pubertal timing on the long-term risk of affective symptoms might be due to different effects of gonadal hormonal on the CNS, as well as different social experiences during puberty

The association between childhood cognitive ability and adult long-term sickness absence in three British birth cohorts: a cohort study

OBJECTIVES: The authors aimed to test the relationship between childhood cognitive function and long-term sick leave in adult life and whether any relationship was mediated by educational attainment, adult social class or adult mental ill-health. DESIGN: Cohort study. SETTING: The authors used data from the 1946, 1958 and 1970 British birth cohorts. Initial study populations included all live births in 1 week in that year. Follow-up arrangements have differed between the cohorts. PARTICIPANTS: The authors included only those alive, living in the UK and not permanent refusals at the time of the outcome. The authors further restricted analyses to those in employment, full-time education or caring for a family in the sweep immediately prior to the outcome. 2894 (1946), 15 053 (1958) and 14 713 (1970) cohort members were included. PRIMARY AND SECONDARY OUTCOME MEASURES: receipt of health-related benefits (eg, incapacity benefit) in 2000 and 2004 for the 1958 and 1970 cohorts, respectively, and individuals identified as 'permanently sick or disabled' in 1999 for 1946 cohort. RESULTS: After adjusting for sex and parental social class, better cognitive function at age 10/11 was associated with reduced odds of being long-term sick (1946: 0.70 (0.56 to 0.86), p=0.001; 1958: 0.69 (0.61 to 0.77), p<0.001; 1970: 0.80 (0.66 to 0.97), p=0.003). Educational attainment appeared to partly mediate the associations in all cohorts; adult social class appeared to have a mediating role in the 1946 cohort. CONCLUSIONS: Long-term sick leave is a complex outcome with many risk factors beyond health. Cognitive abilities might impact on the way individuals are able to develop strategies to maintain their employment or rapidly find new employment when faced with a range of difficulties. Education should form part of the policy response to long-term sick leave such that young people are better equipped with skills needed in a flexible labour market

Childhood chronic physical illness and adult emotional health: a systematic review and meta-analysis

Background: Childhood chronic physical illness is associated with a greater vulnerability for emotional problems (i.e., depression and anxiety) in childhood. However, little is known about life-long effects of childhood chronic physical illness on mental health. The present study aims to systematically review evidence for associations between eight chronic physical illnesses with childhood onset (arthritis, asthma, cancer, chronic renal failure, congenital heart disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional problems. Methods: A database search of MEDLINE, PsycARTICLES, PsycINFO, and ScienceDirect was undertaken, and random effects meta-analyses were used to synthesize evidence from eligible studies. Results: In total, 37 studies were eligible for the systematic review (n = 45,733) and of these, 34 studies were included into the meta-analyses (n = 45,358). There were overall associations between childhood chronic physical illness and adult depression (OR = 1.31; 95% CI [1.12, 1.54]) and anxiety (OR = 1.47; 95% CI [1.13, 1.92]). Separate meta-analyses for childhood asthma, type 1 diabetes and cancer were also conducted, with cancer being significantly associated with adult depression (OR = 1.19; 95% CI [1.00, 1.42]). Conclusions: The effects of childhood chronic physical illness on the risk of emotional problems persist beyond childhood and adolescence. Mental health prevention and intervention strategies targeting children with chronic physical illnesses can have long-term benefits

Comparison of Cognitive Changes in Patients with Alzheimer's and Parkinson's Disease

Objective. —To compare cognitive changes in the dementias of Parkinson's disease (PD) and Alzheimer's disease (AD). Design. —Case series, group comparisons. Setting. —Ambulatory care referral center. Patients. —Consecutive sample of 14 patients with PD dementia and 27 with probable AD matched for overall intellectual function using a mental status test, as well as 1 nondemented PD and 12 mild probable AD patients, similarly matched for overall intellectual function. All demented patients met Diagnostic and Statistical Manual, Revised Third Edition, criteria for dementia. Main Outcome Measures. —Performance on a battery of neuropsychological tests assessing verbal and nonverbal memory, verbal fluency, and constructional ability. Results. —Nondemented and demented patients with PD performed worse than their probable AD comparison groups on verbal fluency and visuospatial tasks. Cognitive changes attributable to dementia were similar in PD and probable AD but were not identical. The patients with probable AD demonstrated more marked change in memory performance with delay. Conclusions. —Our findings suggest that when dementia occurs in PD it is overlaid on cognitive changes that already exist in nondemented patients but that the dementing process in PD involves systems other than those responsible for cognitive change in nondemented PD patients. We hypothesize that in most cases, dementia in PD involves changes in a nondopaminergic neurotransmitter system but is not due to concomitant AD

Cortisol and cognitive function in midlife: the role of childhood cognition and educational attainment

Adult cognition and age-related cognitive decline can be influenced by dysregulation of the hypothalamic pituitary adrenal axis with concomitant changes in cortisol levels. However, very little is known about the role of childhood cognition and educational attainment in this relationship. Using data from the British 1946 birth cohort, the present study investigated: (1) associations between cortisol levels and patterns and cognitive function in midlife; (2) direct and interactive effects of childhood cognition, educational attainment and cortisol on cognitive function in midlife. Verbal memory, letter search speed and reaction time were assessed at age 60-64 years. Salivary cortisol samples (wakening, 30 min after wakening and evening) were collected at the same age. Childhood cognitive ability was measured at ages 8, 11, and 15, and educational level was reported at age 26. Associations between cortisol, childhood cognition, educational attainment and cognitive function in midlife were tested using linear regression and structural equation modelling approaches. Higher evening cortisol level was associated with slower reaction time and lower verbal memory. These associations were independent of childhood cognition and education as well as a range of other potential confounders. Childhood cognition and education were not directly associated with evening cortisol. However, there was a significant interaction effect between childhood cognition and evening cortisol on reaction time (p=.002): higher evening cortisol was associated with slower reaction time only among those with low childhood cognitive ability. There was little evidence of associations between the other cortisol measures and cognitive function

Life course trajectories of affective symptoms and their early life predictors

BACKGROUND: Life course trajectories of affective symptoms (depression and anxiety) are heterogenous. However, few studies have investigated the role of early life risk factors in the development of these trajectories. The present study aimed to: (1) derive latent trajectories of affective symptoms over a period of more than 50 years (ages 13–69), and (2) examine early life risk factors for associations with specific life course trajectories of affective symptoms. METHOD: Participants are from the MRC National Survey of Health and Development (NSHD) (n = 5,362). Affective symptoms were measured prospectively at ages 13, 15, 36, 43, 53, 60–64 and 69. A latent variable modelling framework was implemented to model longitudinal profiles of affective symptoms. Twenty-four prospectively measured early life predictors were tested for associations with different symptom profiles using multinomial logistic regression. RESULTS: Four life course profiles of affective symptoms were identified: (1) absence of symptoms (66.6% of the sample); (2) adolescent symptoms with good adult outcome (15.2%); (3) adult symptoms only (with no symptoms in adolescence and late life) (12.9%); (4) symptoms in adolescence and mid adulthood (5.2%). Of the 24 early life predictors observed, only four were associated with life course trajectories, with small effect sizes observed. CONCLUSIONS: People differ in their life course trajectories of anxiety and depression symptoms and that these differences are not largely influenced by early life factors tested in this study