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.

Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).

A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.

Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.

These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.

Peroxisome Proliferator-Activated Receptor α (PPARα) is a known regulator of lipid and energy metabolism. In animal experiments of PPARα activation, we have reported on altered plasma concentration of metabolites related to one-carbon metabolism and B-vitamin status. Several of these metabolites, e.g. homocysteine and dimethylglycine, have been associated with increased cardiovascular disease risk. Diet can influence one-carbon metabolism, and this may partly be mediated through altered PPARα activity as dietary fatty acids can activate PPARα. As diet is a modifiable life style factor, the aim of this investigation is to explore potential associations between dietary composition and plasma concentration of one-carbon metabolites and markers of B-vitamin status.

The study population consisted of 1977 patients with stable angina (geometric mean age 61 years, 80% male) from the Western Norway B-vitamin Intervention Trial (WENBIT), who completed a self-administered food frequency questionnaire at baseline. Data on outcome variables were obtained from the baseline blood samples (35% fasting). Outcome variables of interest were metabolites related to one-carbon metabolism and B-vitamin status. Cross-sectional associations between protein, carbohydrate and fat intake with the outcome metabolites were analysed with linear regression, adjusted for age, sex, fasting status, BMI and reported energy intake. Estimates are given as % change in the outcome variable per isoenergetic increment of 1 energy % (E%) in the exposure nutrient.

The average distribution [95% prediction interval] of energy intake (E%) in the population was 48.5 (37.1, 63.4) from carbohydrate, 31.4 (21.9, 44.9) from fat and 16.5 (12.2, 22.3) from protein.

The strongest associations were seen for increasing protein intake, while the associations with fat and carbohydrate intake were weaker. The most pronounced associations (% change [95% confidence interval]) with increasing protein intake were higher cobalamin (2.9 [2.1, 3.7]), PLP (2.7 [1.7, 3.7]) and riboflavin (2.3 [1.0, 3.6]), and lower tHcy (-1.4 [-1.9, -0.9]) and MMA (-1.3 [-1.9, -0.7]).

The current observations indicate that dietary macronutrient composition may influence plasma concentration of one-carbon metabolites and markers of B-vitamin status. The strongest associations are observed with increasing protein intake, but elucidating the importance of the nutrient substituted remains. Whether the observed associations are due to macronutrients per se, or reflect differences in food choices/nutrient intakes, or effects on physiological factors, i.e. inflammation or PPARα activation, is not known.

Women suffering from first onset postpartum mental disorders (PPMD) have a highly elevated risk of suicide. The current study aimed to: (1) describe the risk of self-harm among women with PPMD and (2) investigate the extent to which self-harm is associated with later suicide.

We conducted a register-based cohort study linking national Danish registers. This identified women with any recorded first inpatient or outpatient contact to a psychiatric facility within 90 days after giving birth to their first child. The main outcome of interest was defined as the first hospital-registered episode of self-harm. Our cohort consisted of 1 202 292 women representing 24 053 543 person-years at risk.

Among 1554 women with severe first onset PPMD, 64 had a first-ever hospital record of self-harm. Women with PPMD had a hazard ratio (HR) for self-harm of 6.2 (95% CI 4.9–8.0), compared to mothers without mental disorders; but self-harm risk was lower in PPMD women compared to mothers with non-PPMD [HR: 10.1, (95% CI 9.6–10.5)] and childless women with mental disorders [HR: 9.3 (95% CI 8.9–9.7)]. Women with PPMD and records of self-harm had a significantly greater risk for later suicide compared with all other groups of women in the cohort.

Women with PPMD had a high risk of self-harm, although lower than risks observed in other psychiatric patients. However, PPMD women who had self-harmed constituted a vulnerable group at significantly increased risk of later suicide.

To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.

Memory clinics and dementia services.

Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).

Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.

There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).

There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.

Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.

We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.

The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).

Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).

Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.

MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.

MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.

Congenital heart defect patients may experience neurodevelopmental impairment. We investigated their educational attainments from basic schooling to higher education.

Using administrative databases, we identified all Danish patients with a cardiac defect diagnosis born from 1 January, 1977 to 1 January, 1991 and alive at age 13 years. As a comparison cohort, we randomly sampled 10 persons per patient. We obtained information on educational attainment from Denmark's Database for Labour Market Research. The study population was followed until achievement of educational levels, death, emigration, or 1 January, 2006. We estimated the hazard ratio of attaining given educational levels, conditional on completing preceding levels, using discrete-time Cox regression and adjusting for socio-economic factors. Analyses were repeated for a sub-cohort of patients and controls born at term and without extracardiac defects or chromosomal anomalies.

We identified 2986 patients. Their probability of completing compulsory basic schooling was approximately 10% lower than that of control individuals (adjusted hazard ratio = 0.79, ranged from 0.75 to 0.82 0.79; 95% confidence interval: 0.75–0.82). Their subsequent probability of completing secondary school was lower than that of the controls, both for all patients (adjusted hazard ratio = 0.74; 95% confidence interval: 0.69–0.80) and for the sub-cohort (adjusted hazard ratio = 0.80; 95% confidence interval: 0.73–0.86). The probability of attaining a higher degree, conditional on completion of youth education, was affected both for all patients (adjusted hazard ratio = 0.88; 95% confidence interval: 0.76–1.01) and for the sub-cohort (adjusted hazard ratio = 0.92; 95% confidence interval: 0.79–1.07).

The probability of educational attainment was reduced among long-term congenital heart defect survivors.