Neuropsychiatric symptoms (NPS) are the leading cause of the social burden of dementia but their role is underestimated.

The objective of the study was to validate predictive models to separately identify psychotic and depressive symptoms in patients diagnosed with dementia using clinical databases representing the whole population to inform decision-makers.

First, we searched the electronic health records of 4,003 patients with dementia to identify NPS. Second, machine learning (random forest) algorithms were applied to build separate predictive models for psychotic and depressive symptom clusters in the training set (N = 3,003). Third, calibration and discrimination were assessed in the test set (N = 1,000) to assess the performance of the models.

Neuropsychiatric symptoms were noted in the electronic health record of 58% of patients. The area under the receiver operating curve reached 0.80 for the psychotic cluster model and 0.74 for the depressive cluster model. The Kappa index and accuracy also showed better discrimination in the psychotic model. Calibration plots indicated that both types of model had less predictive accuracy when the probability of neuropsychiatric symptoms was <25%. The most important variables in the psychotic cluster model were use of risperidone, level of sedation, use of quetiapine and haloperidol and the number of antipsychotics prescribed. In the depressive cluster model, the most important variables were number of antidepressants prescribed, escitalopram use, level of sedation, and age.

Given their relatively good performance, the predictive models can be used to estimate prevalence of NPS in population databases.

Given their relatively good performance, the predictive models can be used to estimate prevalence of NPS in population databases.

The choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, was recently identified as an important component of the circadian clock system.

The fact that circadian rhythm disruption is closely associated to Alzheimer’s disease (AD) led us to investigate whether AD pathology can contribute to disturbances of the circadian clock in the CP.

For this purpose, we evaluated the expression of core-clock genes at different time points, in 6- and 12-month-old female and male APP/PS1 mouse models of AD. In addition, we also assessed the effect of melatonin pre-treatment in vitro before amyloid-β stimulus in the daily pattern of brain and muscle Arnt-like protein 1 (Bmal1) expression.

Our results showed a dysregulation of circadian rhythmicity of Bmal1 expression in female and male APP/PS1 transgenic 12-month-old mice and of Period 2 (Per2) expression in male mice. In addition, a significant circadian pattern of Bmal1 was measured the intermittent melatonin pre-treatment group, showing that melatonin can reset the CP circadian clock.

These results demonstrated a connection between AD and the disruption of circadian rhythm in the CP, representing an attractive target for disease prevention and/or treatment.

These results demonstrated a connection between AD and the disruption of circadian rhythm in the CP, representing an attractive target for disease prevention and/or treatment.

The link between cholesterol and Alzheimer’s disease (AD) has received much attention, as evidence suggests high levels of cholesterol might be an AD risk factor. selleck kinase inhibitor The carriage of cholesterol and lipids through the body is mediated via lipoproteins, some of which, particularly apolipoprotein E (ApoE), are intimately linked with AD. In humans, high density lipoprotein (HDL) is regarded as a “good” lipid complex due to its ability to enable clearance of excess cholesterol via ‘cholesterol reverse transport’, although its activities in the pathogenesis of AD are poorly understood. There are several subclasses of HDL; these range from the newly formed small HDL, to much larger HDL.

We examined the major subclasses of HDL in healthy controls, mild cognitively impaired, and AD patients who were not taking statins to determine whether there were HDL profile differences between the groups, and whether HDL subclass levels correlated with plasma amyloid-β (Aβ) levels or brain Aβ deposition.

Samples from AIBL cohort were used in this study. HDL subclass levels were assessed by Lipoprint while Aβ1-42 levels were assessed by ELISA. Brain Aβ deposition was assessed by PET scan. Statistical analysis was performed using parametric and non-parametric tests.

We found that small HDL subclass is reduced in AD patients and it correlates with cognitive performance while plasma Aβ concentrations do not correlate with lipid profile or HDL subfraction levels.

Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances.

Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances.

Alzheimer’s disease (AD) etiopathogenesis remains partially unexplained. The main conceptual framework used to study AD is the Amyloid Cascade Hypothesis, although the failure of recent clinical experimentation seems to reduce its potential in AD research.

A possible explanation for the failure of clinical trials is that they are set too late in AD progression. Recent studies suggest that the ventral tegmental area (VTA) degeneration could be one of the first events occurring in AD progression (pre-plaque stage).

Here we investigate this hypothesis through a computational model and computer simulations validated with behavioral and neural data from patients.

We show that VTA degeneration might lead to system-level adjustments of catecholamine release, triggering a sequence of events leading to relevant clinical and pathological signs of AD. These changes consist first in a midfrontal-driven compensatory hyperactivation of both VTA and locus coeruleus (norepinephrine) followed, with the progression of the VTA impairment, by a downregulation of catecholamine release. These processes could then trigger the neural degeneration at the cortical and hippocampal levels, due to the chronic loss of the neuroprotective role of norepinephrine.

Our novel hypothesis might contribute to the formulation of a wider system-level view of AD which might help to devise early diagnostic and therapeutic interventions.

Our novel hypothesis might contribute to the formulation of a wider system-level view of AD which might help to devise early diagnostic and therapeutic interventions.