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Cilostazol may be a novel therapeutic agent for Alzheimer's disease. Its metabolite, OPC-13015, has a stronger inhibitory effect on type 3 phosphodiesterase than cilostazol.

We prospectively enrolled patients with mild cognitive impairment to whom cilostazol was newly prescribed. VX-661 Patients underwent the Montreal Cognitive Assessment (MoCA) twice, at a 6-month interval. Plasma cilostazol, OPC-13015, OPC-13213, and OPC-13217 concentrations were determined using liquid chromatography-tandem mass spectrometry.

MoCA score changes from baseline to the 6-month visit were positively correlated with ratios of OPC-13015 to cilostazol and total metabolites (
=19,
=.005). Patients with higher ratios of OPC-13015 (≥0.18, median value;
=10) had significantly higher MoCA scores (
=.036) than patients with lower ratios (the ratio<0.18,
=9). The absolute value of OPC-13015 concentration in blood was also higher in patients with preserved cognitive function (
=.033).

Blood OPC-13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.
Blood OPC-13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.
The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD.

We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials.

There are 126 agents in 152 trials assessing new therapies for AD 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms.

This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.
This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.
One of the major hallmarks of Alzheimer's disease (AD)is the aberrant modification and aggregation of the microtubule-associated protein Tau . The extent of Tau pathology correlates with cognitive decline, strongly implicating Tau in the pathogenesis of the disease. Because the inhibition of Tau aggregation may be a promising therapeutic target, we tested the efficacy of BSc3094, an inhibitor of Tau aggregation, in reducing Tau pathology and ameliorating the disease symptoms in transgenic mice.

Mice expressing human Tau with the P301L mutation (line rTg4510) were infused with BSc3094 into the lateral ventricle using Alzet osmotic pumps connected to a cannula that was placed on the skull of the mice, thus bypassing the blood-brain barrier (BBB) . The drug treatment lasted for 2 months, and the effect of BSc3094 on cognition and on reversing hallmarks of Tau pathology was assessed.

BSc3094 significantly reduced the levels of Tau phosphorylation and sarkosyl-insoluble Tau. In addition, the drug improved cognition in different behavioral tasks and reduced anxiety-like behavior in the transgenic mice used in the study.

Our in vivo investigations demonstrated that BSc3094 is capable of partially reducing the pathological hallmarks typically observed in Tau transgenic mice, highlighting BSc3094 as a promising compound for a future therapeutic approach for AD.
Our in vivo investigations demonstrated that BSc3094 is capable of partially reducing the pathological hallmarks typically observed in Tau transgenic mice, highlighting BSc3094 as a promising compound for a future therapeutic approach for AD.
Person-centered care and assessment calls for measurement tools that help researchers and providers understand people with dementia, their social relationships, and their experience of the care environment. This paper reviewed available measures and evaluated their psychometric properties.

Literature searches of major databases (PsycInfo, PubMed, EBSCO, CINAHL) for papers examining person-centered constructs in samples of people living with dementia or mild cognitive impairment. Reliability and validity coefficients were reviewed and reported.

We identified 26 unique measures that had been tested in samples of people living with dementia. Twelve measures of hope, well-being, engagement, social relationships, meaning, resilience, stigma, spiritual beliefs and practices, values and preferences, and positive psychology constructs had strong psychometric properties in samples with dementia.

A variety of reliability and valid measures were identified for use in person-centered care and research with people living with dementia. Additional measure development is needed for key person-centered concepts including dignity and strengths.
A variety of reliability and valid measures were identified for use in person-centered care and research with people living with dementia. Additional measure development is needed for key person-centered concepts including dignity and strengths.
A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis.

MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35mg/day intepirdine or placebo for 24weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL).

There were no statistically significant differences between intepirdine and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (-0.36 [-0.95, 0.22],
=0.2249) and ADCS-ADL (-0.09 [-0.90, 0.72],
=0.8260). Intepirdine demonstrated a favorable safety profile similar to placebo.

Intepirdine as adjunctive therapy to donepezil did not produce statistical improvement over placebo on cognition or activities of daily living in mild-to-moderate AD dementia patients.
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