Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-ß protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

In vitro evaluation of Kedo-S and RaCe rotary files compared to hand files in preparing the root canals of primary molar teeth.

BACKGROUND AND AIMS: Considering the advantages of rotary files in instrumenting the root canals of permanent teeth and a lack of adequate data on the use of these systems in primary teeth, the present study aimed to evaluate two rotary files and compare them with hand files in the cleaning efficacy of the root canals of primary molar teeth. MATERIALS AND METHODS: In the present study, three groups of teeth were prepared with Kedo-S paediatric rotary file system, RaCe (reamer with alternating cutting edges), and hand files (n = 40). The groups were evaluated under a stereomicroscope concerning the cleaning efficacy of the files after cleaning the teeth in the apical, middle, and coronal thirds. The data were analyzed with SPSS 24 (IBM Corporation, USA, 2016) using Fisher's exact test and chi-squared test; statistical significance was set at p < 0.05. RESULTS: There were no significant differences in the apical and middle thirds between the different study groups. However, there were significant differences in the coronal third between the hand file and Kedo-S (p = 0.016) and RaCe and Kedo-S (p = 0.001) groups. CONCLUSIONS: The present study showed that Kedo-S files were more effective than RaCe and hand files in the coronal area than the hand and RaCe files.