Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.

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Patterns of plasma ACTH and cortisol concentrations were studied in 10 healthy subjects (five male, five female in the early follicular phase, overall age range 21-32 years) by sampling through an indwelling cannula every 15 min for 24 h. The subjects were in hospital, ambulant, and taking normal meals. Plasma ACTH was measured by a two-site immunoradiometric assay with a detection limit of 3.9 ng/l (0.9 pmol/l). Pulses were identified by the method of Clayton et al. (1987) using stringent criteria to minimize false positive peaks. All subjects showed a circadian rhythm of ACTH, the acrophase occurring between 0615 and 0920 h in all but one subject and the mesor value was between 9.2 and 18.6 ng/l (2.0 and 4.1 pmol/l). There were significantly fewer pulses between 1800 and 2400 h compared with the other three 6-h periods. The pattern of ACTH differed between males and females in several respects: more pulses (18 vs 10), greater mean peak amplitude (16.8 vs 10.3 ng/l), greater area under the 24-h profile (350.9 vs 206.6 ng/l h) and higher mean level (14.7 vs 8.6 ng/l) in the males. In contrast, the cortisol pattern did not show statistically different sex differences. The sex differences suggest greater sensitivity to, or availability of, ACTH to the female adrenal cortex, or different set points in cortisol feedback.

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