Are NSAIDs Useful to Treat Alzheimer's Disease or Mild Cognitive Impairment?

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4) against the onset of Alzheimer's disease (AD). The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ) cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2) selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial) of naproxen (a non-selective COX inhibitor) and celecoxib (a COX-2 selective inhibitor) in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after 2 years of treatment, a 4-year follow-up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers

Dietary Patterns Associated with Alzheimer’s Disease: Population Based Study

Recently dietary pattern analysis has emerged as a way for examining diet-disease relations in Alzheimer’s disease. In contrast with the conventional approach, which focuses on a single nutrient or a few nutrients or foods, this method considers overall eating patterns. We examined the dietary patterns defined by factor analysis using data collected with a food-frequency questionnaire in people with Alzheimer’s disease (AD) as compared to healthy controls. The diet data were obtained during population based study of the prevalence of Alzheimer’s disease in a population in Poland. Stratified sampling and random selection strategies were combined to obtain a representative population for screening (age group > 55). From the population screened three times, 71 people were diagnosed with Alzheimer’s according to DSM-IV, and were recruited for further diet risk factors assessment. A group of people with Alzheimer disease (n = 71; F/M 42/29) and the same number of healthy, age and gender matched control were recruited for the study. Patients and their caregivers as well as controls were presented with a food frequency questionnaire based on the 12 food groups. Factor analysis (principal component) was used to derive food patterns. The analysis was conducted using the factor procedure. The factors were rotated by an orthogonal transformation (Varimax rotation) to achieve simpler structure with greater interpretability. Using factor analysis, we identified major eating patterns, one for Alzheimer’s patients and a different one for control group. The AD dietary pattern, FACTOR AD was characterized by a high intake of meat, butter, high-fat dairy products, eggs, and refined sugar, whereas the other pattern, (FACTOR C) was characterized by a high intake of grains and vegetables. These data indicate the existence of dietary patterns defined by factor analysis with data from a food frequency questionnaire, characteristic for Alzheimer’s disease in a Polish population

Carotenoids and cognitive outcomes: A meta-analysis of randomized intervention trials

Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid sup-plementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured out-comes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carote-noid intervention on cognitive outcomes (Hedge’s g = 0.14; 95 % confidence interval: 0.08, 0.20, p < 0.0001). There was no evidence of heterogeneity among the studies (τ2 = 0.00, I2 = 0.00%, H2 = 1.00) or publication bias. Although further studies are needed, our results suggest that carotenoid interventions are associated with better cognitive performance. Thus, these dietary compounds may help to reduce the risk of cognitive impairment and dementia

Role of Olive Oil and Monounsaturated Fatty Acids in Mitochondrial Oxidative Stress and Aging

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Alternative pharmacological treatment options for agitation in Alzheimer's disease

In patients with dementia and Alzheimer's disease (AD), treatment of neuropsychiatric symptoms (NPS) is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs), with disappointing results. However, evidence coming from recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/ quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia

Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene

Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies

ACOUSTIC ANALYSIS OF SWALLOWING SOUNDS: A NEW TECHNIQUE FOR ASSESSING DYSPHAGIA

Objective: To perform acoustic analysis of swallowing sounds, using a microphone and a notebook computer system, in healthy subjects and patients with dysphagia affected by neurological diseases, testing the positive/negative predictive value of a pathological pattern of swallowing sounds for penetration/aspiration. Design: Diagnostic test study, prospective, not blinded, with the penetration/aspiration evaluated by fibreoptic endo scopy of swallowing as criterion standard. Subjects: Data from a previously recorded database of normal swallowing sounds for 60 healthy subjects according to gender, age, and bolus consistency was compared with those of 15 patients with dysphagia from a university hospital referral centre who were affected by various neurological diseases. Methods: Mean duration of the swallowing sounds and postswallowing apnoea were recorded. Penetration/aspiration was verified by fibreoptic endoscopy of swallowing in all patients with dysphagia. Results: The mean duration of swallowing sounds for a liquid bolus of 10 ml water was significantly different between patients with dysphagia and healthy patients. We also described patterns of swallowing sounds and tested the negative/positive predictive values of post-swallowing apnoea for penetration/aspiration verified by fibreoptic endoscopy of swallowing (sensitivity 0.67 (95% confidence interval 0.24–0.94); specificity 1.00 (95% confidence interval 0.56–1.00)). Conclusion: The proposed technique for recording and measuring swallowing sounds could be incorporated into the bedside evaluation, but it should not replace the use of more diagnostic and valuable measures

effect of intrathecal baclofen botulinum toxin type a and a rehabilitation programme on locomotor function after spinal cord injury a case report

Objective: a few studies have reported the use of botulinum toxin injections after spinal cord injury, as this is the gold standard to treat focal spasticity. We report such a case here. Case report: a 38-year-old woman who had become paraplegic and care-dependent secondary to cervico-thoracic intramedullary ependymoma, presented 8 months later with painful lower limb spasticity, which was being treated with oral anti-spastic and benzodiazepine drugs with no therapeutic effect. We treated the patient with intrathecal baclofen to reduce her spasticity and in order to avoid the major side-effects of high dosages of oral baclofen. after motor rehabilitation programmes, which included functional ele

Vascular risk and genetics of sporadic late-onset Alzheimer's disease.

In recent years, it is becoming apparent that genes may play an important role in the development of late-onset Alzheimer’s disease (LOAD), and genetic studies could unravel new clues. Based on a growing vascular hypothesis for the pathogenesis of LOAD and other dementias, there is increasing interest for environmental and genetic vascular factors. Polymorphisms in different susceptibility genes already implicated in vascular disease risk are now also being suggested as possible genetic markers for increased risk of developing LOAD; however, many of these studies have shown conflicting results. Thus far, the apolipoprotein E (APOE) gene seems to be the only vascular susceptibility factor that is agreed to play a role in the multifactorial pathogenesis of AD although emerging genetic and biological evidence is now strengthening the case for additional inclusion of angiotensin I-converting enzyme 1 (ACE1) into this category. This review will focus on the current knowledge on genetic and nongenetic vascular factors likely to be involved in LOAD, with special emphasis placed on the APOE and ACE1 genes