Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (N=967) was assessed to control for practice effects. For episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.

Stability, growth, and decline in adult life span development of declarative memory: cross-sectional and longitudinal data from a population-based study.

OBJECTIVES: To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline. DESIGN: Prospective cohort study. At study inception in 1985-8, there were 10,308 participants, representing a recruitment rate of 73%. SETTING: Civil service departments in London, United Kingdom. PARTICIPANTS: 5198 men and 2192 women, aged 45-70 at the beginning of cognitive testing in 1997-9. MAIN OUTCOME MEASURE: Tests of memory, reasoning, vocabulary, and phonemic and semantic fluency, assessed three times over 10 years. RESULTS: All cognitive scores, except vocabulary, declined in all five age categories (age 45-49, 50-54, 55-59, 60-64, and 65-70 at baseline), with evidence of faster decline in older people. In men, the 10 year decline, shown as change/range of test × 100, in reasoning was -3.6% (95% confidence interval -4.1% to -3.0%) in those aged 45-49 at baseline and -9.6% (-10.6% to -8.6%) in those aged 65-70. In women, the corresponding decline was -3.6% (-4.6% to -2.7%) and -7.4% (-9.1% to -5.7%). Comparisons of longitudinal and cross sectional effects of age suggest that the latter overestimate decline in women because of cohort differences in education. For example, in women aged 45-49 the longitudinal analysis showed reasoning to have declined by -3.6% (-4.5% to -2.8%) but the cross sectional effects suggested a decline of -11.4% (-14.0% to -8.9%). CONCLUSIONS: Cognitive decline is already evident in middle age (age 45-49).

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Timing of Onset of Cognitive Decline: Results from Whitehall II Prospective Cohort Study

Background: Little is known on the adult outcome and longitudinal trajectory of childhood developmental language disorders (DLD) and on the prognostic predictors.

Method:  Seventeen men with a severe receptive DLD in childhood, reassessed in middle childhood and early adult life, were studied again in their mid-thirties with tests of intelligence (IQ), language, literacy, theory of mind and memory together with assessments of psychosocial outcome. They were compared with the non language disordered siblings of the DLD cohort to control for shared family background, adults matched to the DLD cohort on age and performance IQ (IQM group) and a cohort from the National Child Development Study (NCDS) matched to the DLD cohort on childhood IQ and social class.

Results:  The DLD men had normal intelligence with higher performance IQ than verbal IQ, a severe and persisting language disorder, severe literacy impairments and significant deficits in theory of mind and phonological processing. Within the DLD cohort higher childhood intelligence and language were associated with superior cognitive and language ability at final adult outcome. In their mid-thirties, the DLD cohort had significantly worse social adaptation (with prolonged unemployment and a paucity of close friendships and love relationships) compared with both their siblings and NCDS controls. Self-reports showed a higher rate of schizotypal features but not affective disorder. Four DLD adults had serious mental health problems (two had developed schizophrenia).

Conclusion:  A receptive developmental language disorder involves significant deficits in theory of mind, verbal short-term memory and phonological processing, together with substantial social adaptation difficulties and increased risk of psychiatric disorder in adult life. The theoretical and clinical implications of the findings are discussed.

Developmental language disorders – a follow-up in later adult life. Cognitive, language and psychosocial outcomes

Chronic stress, cognitive functioning and mental health

Rubin's multiple imputation is a three-step method for handling complex missing data, or more generally, incomplete-data problems, which arise frequently in medical studies. At the first step, m (>...

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Applications of multiple imputation in medical studies: from AIDS to NHANES

Identifying and separating the effects of practice and of cognitive ageing during a large longitudinal study of elderly community residents.

We propose an alternative to the method of generalized estimating equations (GEE) for inference about binary longitudinal data. Unlike GEE, the method is practicable when the data consist of long time series on each subject and the set of observation times is not necessarily common to all subjects. Instead of modelling the intra-series correlations explicitly, we assume that a subject's propensity to respond is governed by an underlying, but unobserved, stationary continuous process. Given a realization of this process, we assume that the binary responses are conditionally independent, with the probability that a subject responds positively at any given time t depending on the value of the underlying process at that time and also on any covariates specific to the subject at that time. We develop an algorithm for estimating the parameters in this model, and investigate its effectiveness using simulation methods. We also apply the methodology to data collected in a trial investigating the effect of self-measurement of blood pressure on compliance in taking medication during a course of anti-hypertension treatment.

Compliance in an anti‐hypertension trial: a latent process model for binary longitudinal data

A clinical trial of an analgesic agent compares pain relief scores over time among groups of patients. All subjects experience the same painful procedure, but different subjects are given different randomly assigned doses of active agent or placebo when they first request it. The data are short individual time series of ordered categorical pain relief scores subsequent to dosing. Nonrandom right censoring may be present because patients can elect to remedicate with an active agent if their pain relief is insufficient. The trial is meant to address two questions: (a) Is there proof that the drug relieves pain? If so, (b) What dosage patterns should be investigated further, or recommended for use by a typical patient? Marginal models of human pharmacology are basically empirical models, and although an analysis of a study based on such a model can adequately address the first question, such is not the case for the second question, because this question requires extrapolation to untested dosing patterns. We propose to analyze study data using a hierarchical model so as to address both questions. The analysis uses a semimechanistic subject-specific pain-relief model for the distribution of all (uncensored and censored) observations, conditional on individual random effects, and an empirical model for the censoring outcome, remedication, conditional on observed pain relief and individual random effects. We estimate the parameters of the foregoing (nonlinear mixed effects) model via maximum likelihood, assuming normally distributed random effects. Monte Carlo integration with respect to the random effects is used to compute marginal statistics relevant to the dosing question. Of particular note is that this formulation encourages use of subject matter information in model specification so that the extrapolations required to address the dosing question are credible. An example is given of the application of the analysis to analgesic trial data for the drug ketorolac.

David M. Smith

Papers

Identifying and separating the effects of practice and of cognitive ageing during a large longitudinal study of elderly community residents.

Compliance in an anti‐hypertension trial: a latent process model for binary longitudinal data

Analysis of Nonrandomly Censored Ordered Categorical Longitudinal Data from Analgesic Trials: Comment