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Alzheimer’s disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit. More recently, protective effects of diclofenac and NSAIDs in the fenamate group have been reported. Diclofenac decreased the frequency of AD significantly compared to other NSAIDs in a large retrospective cohort study. Diclofenac and fenamates share similar chemical structures, and evidence from cell and mouse models suggests that they inhibit the release of pro-inflammatory mediators from microglia with leads to the reduction of AD pathology. Here, we review the potential role of diclofenac and NSAIDs in the fenamate group for targeting AD pathology with a focus on its potential effects on microglia.

Background Recent data indicate that the three-month prevalence of severe headaches or migraines in the US general population is close to 25%. Participation of primary care providers will therefore be critical in providing care to affected individuals. Objective To determine the number of headache disorder consult requests to a neurology outpatient service in a tertiary medical center, the appropriateness of the consult requests, and the effectiveness of a lecture series on headache diagnosis and management in preventing inappropriate consult requests from non-neurology providers. Methods Clinical data on US Veterans is captured and documented in the Veterans Health Information Systems and Technology Architecture (VISTA). The Computerized Patient Record System (CPRS) electronic medical record (EMR) was used for data entry and retrieval. All consult requests for the study period within the VA North Texas Health Care System were identified in VISTA, and the clinical information reviewed in CPRS. Based on a defined algorithm, headache consult request were categorized as appropriate or inappropriate. A board-certified neurologist provided four in-person/virtual lectures to ambulatory care providers, primary care providers, internal medicine residents, and emergency room providers within the VA North Texas Health Care System on the diagnosis and management of headaches. Prior and post the lecture series, the total number of headache consults per day was assessed over 45-day periods. Results The number of daily headache consult requests in the 45-day period prior to the lecture series was 3.6 per day (standard deviation 2.7), and 6.0 per day after the lecture series (standard deviation 2.1). The difference was not statistically significant. There were as many inappropriate headache consult requests after the lecture series as appropriate ones (50% each). Conclusion We found that a short-term educational initiative that instructed primary care providers on the diagnosis and management of common headache disorders did not reduce the number of consultation requests and, surprisingly, it did not improve the appropriateness of the consults. Given the prevalence of headaches in the general population, better training of all primary care providers in headache management should be pursued.

Background: Our aim was to determine whether specific nonsteroidal anti-inflammatory (NSAID) agents are associated with a decreased frequency of Alzheimer’s disease (AD). Materials and methods: Days of drug exposure were determined for diclofenac, etodolac, and naproxen using US Department of Veterans Affairs (VA) pharmacy transaction records, combined from two separate VA sites. AD diagnosis was established by the International Classification of Diseases, ninth revision (ICD-9)/ICD-10 diagnostic codes and the use of AD medications. Cox regression survival analysis was used to evaluate the association between AD frequency and NSAID exposure over time. Age at the end of the study and the medication-based disease burden index (a comorbidity index) were used as covariates. Results: Frequency of AD was significantly lower in the diclofenac group (4/1431, 0.28%) compared with etodolac (328/14,646, 2.24%), and naproxen (202/12,203, 1.66%). For regression analyses, naproxen was chosen as the comparator drug, since it has been shown to have no effect on the development of AD. Compared with naproxen, etodolac had no effect on the development of AD, hazard ratio (HR) 1.00 [95% confidence interval (CI): 0.84–1.20, p = 0.95]. In contrast, diclofenac had a significantly lower HR of AD compared with naproxen, HR 0.25 (95% CI: 0.09–0.68, p