A multidimensional frailty approach in predicting and preventing dementia

n/

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

Non-Pharmacological Approaches in the Treatment of Dementia

Currently, a pharmacological disease-modifying treatment for dementia is not available, but different non-pharmacological approaches appear to be useful. In this chapter, we describe traditional treatments such as cognitive and emotion-oriented interventions, sensory and multi-sensory stimulation interventions and also potentially alternative interesting options such as behavioural therapy, animal-assisted therapy, home-adaptation therapy and assistive technologies to support patient with dementia. Many non-pharmacological treatments have reported benefits in multiple research studies, but there is a need for further Randomized controlled trials (RCTs) with an adequate sample size to improve the strength of evidence in order to apply these approaches

Information and Communication Technologies for the Activities of Daily Living in Older Patients with Dementia: A Systematic Review

Background: Significant innovations have been introduced in recent years in the application of information and communication technologies (ICTs) to support healthcare for patients with dementia. Objective: In the present systematic review, our goal is to keep track of ICT concepts and approaches to support the range of activities of daily living for people with dementia and to provide a snapshot of the effect that technology is having on patients' self-reliance. Methods: We reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. Our selection criteria included: (1) activities of daily living, (2) ICT, and (3) dementia. Results: We identified 56 studies published between 2000 and 2015, of which 26 met inclusion criteria. The present systematic review revealed many ICT systems that could purportedly support the range of activities of daily living for patients with dementia. The results showed five research bodies: 1) technologies used by patients with dementia, 2) technologies used by caregivers, 3) monitoring systems, 4) ambient assistive living with ICTs, and 5) tracking and wayfinding. Conclusions: There is a potential for ICTs to support dementia care at home and to improve quality of life for caregivers, reducing healthcare costs and premature institutional care for these patients

Sensory impairments and cognitive disorders in older age

Age-related and neuropathological changes in the olfactory, visual, auditory, and motor systems suggesting that sensory and motor changes may precede the cognitive symptoms of Alzheimer’s disease (AD) by several years and may signify increase the risk of developing AD. In particular, peripheral age-related hearing impairment and social isolation have been identified as potentially modifiable dementia risk factors. The impact of age-related hearing and vision impairments on cognition appeared to be especially important among the oldest old suggesting a strong link of these connections with frailty, a critical intermediate status of the aging process at higher risk for negative health-related outcomes. The link among age-related hearing and vision impairments and cognition suggested the potential for correcting hearing and vision losses so that older subjects can function better cognitively with improved social involvement, quality of life, and lifetime cognitive health

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