In the current climate of an ageing population, it is imperative to identify preventive measures for dementia.

We implemented a multifaceted index of cognitive reserve markers and investigated dementia incidence over 15 years of follow-up in a representative sample of the English population.

Data were 12 280 participants aged ≥50 years from the English Longitudinal Study of Ageing, free from dementia at their baseline assessments during wave 1 (2002–2003), 3 (2006–2007) or 4 (2008–2009), and followed up until wave 8 (2016–2017). The Cognitive Reserve Index was constructed as a composite measure of education, occupation and leisure activities, using a standardised questionnaire. Cox proportional hazards regression models were used to estimate the hazard ratios of dementia in relation to cognitive reserve levels (low, medium and high) and its components (education, occupation and leisure activities).

During the follow-up period, 602 participants aged 56–99 years developed dementia. Higher levels of cognitive reserve (hazard ratio 0.65, 95% CI 0.48–0.89, P = 0.008) were associated with a lower risk of dementia. An individual analysis of its components showed that higher levels of education (hazard ratio 0.56, 95% CI 0.36–0.88, P = 0.012), occupation (hazard ratio 0.72, 95% CI 0.56–0.91, P = 0.008) and leisure activities (hazard ratio 0.74, 95% CI 0.56–0.99, P = 0.047) were predictive of a reduced dementia risk, with the first two components particularly protective in younger participants (<85 years).

This study showed a reduced risk of dementia for individuals with a higher level of cognitive reserve, represented by higher education, complex occupations and multifaceted level of leisure activities.

Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined.

To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition.

Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50.

After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (β = −0.002, s.e. = 0.001, P = 0.009), delayed memory (β = −0.002, s.e. = 0.001, P = 0.02) and verbal fluency (β = −0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk.

These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.

The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline.

To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date.

We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling.

The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2–5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment.

This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.

In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.

This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).

A statistical model, which described the concentration–time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.

The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann–Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.

Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.

Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.

To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.

We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.

At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.

It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.