Current Clinical Pharmacology - Volume 10, Issue 3, 2015

Older adults with dementia commonly have multiple chronic conditions that prompt clinicians to prescribe medications. While dementia is a life-limiting disease, progression from mild cognitive impairment to end stage dementia is a process that can occur over many years and may not take a predetermined course. Therefore aligning pharmacological treatment with changing goals of care can be challenging. The aim of this narrative review was to explore barriers to optimising prescribing and deprescribing (withdrawing) of medications as the goal of care shifts from prolonging life to optimising quality of life. Optimising pharmacological treatment to help people with dementia achieve their goals of care often requires deprescribing of medications that are inappropriate, as well as initiating appropriate medications. Medical practitioner, system, patient and carer related barriers to optimisation of medications in older adults with multiple morbidities have been identified including: inadequate guidelines, incomplete medical histories, lack of time, avoidance of negative consequences, established beliefs in the benefits and harms of medication use and others. Optimising prescribing for older people with dementia is further complicated by diminished decision making capacity, difficulties with comprehension and communication, increasing involvement of carers and difficulties establishing goals of care. Further research is required into the attitudes, beliefs and preferences of people with dementia and their carers regarding prescribing and deprescribing.

The aim of this systematic review was to identify, assess and summarize studies about potentially inappropriate drug use (IDU) in cognitive impairment and dementia and to present findings about whether cognitive impairment and dementia are associated with IDU. The search was made in Medline/PubMed using free terms in the title or abstract. The inclusion criteria were: English language, published until 1 March 2014, original quantitative study and assessment of overall IDU with a consensus based summarized measure. Exclusion criteria were: focus on specific patient group (other than cognitive impairment or dementia), focus on specific drug class and failure to present a prevalence measure of IDU or an effect estimate (i.e. odds ratio). Of the initial 182 studies found in Medline, 22 articles fulfilled the criteria. Most studies used the Beers criteria for assessment of IDU. Prevalence of IDU among individuals with cognitive impairment or dementia ranged from 10.2% to 56.4% and was higher in nursing home settings than in community-dwelling samples. Most studies reported a lower likelihood of IDU in case of cognitive impairment or dementia. To conclude, IDU is highly prevalent among persons with cognitive impairment and dementia, although these conditions seem to be associated with a lower probability of IDU. This might reflect an awareness among clinicians of cautious prescribing to this vulnerable group of patients. More studies on large cohorts of persons with cognitive impairment and dementia are needed to draw conclusions about optimal drug prescribing to this frail group of older persons.

Whether to start, continue or discontinue statins in older people remains a clinical and ethical dilemma. While there is clinical trial evidence that statins reduce cardiovascular morbidity in older people, recently concerns have been raised about side effects in this population. Adverse effects of statins reported in older people include muscle-related symptoms, diabetes, impaired physical function and cognitive impairment. The cognitive effects of statins are not well understood and remain contentious. In younger and healthier people with baseline intact cognitive function, short-term data suggest no adverse effects of statins on cognition whereas long-term data support a beneficial role for statins in delaying dementia. Insufficient evidence is currently available to establish causality in relation to statins and cognitive function in older people specifically. The objective of this narrative review is to analyse the current evidence in relation to statin therapy and cognition, and discuss challenges in translating the current evidence to older people.

Pain is a frequent cause of discomfort and distress in residents in residential aged care facilities (RACFs). Despite the benefits of adequate pain management, there is inconsistency in the literature regarding analgesic use and pain in residents with dementia. The aim of this systematic review was to determine the prevalence of analgesic drug use among residents with and without dementia or cognitive impairment in RACFs. A systematic search of MEDLINE and EMBASE (inception to January 2014) was conducted using Medical Subject Headings and Emtree terms, respectively. Studies were included if they reported prevalence of analgesic use for residents both with and without dementia within the same study. Data extraction and quality assessment was performed independently by two investigators. Data on the prevalence of analgesic use, pain and painful conditions were extracted. Meta-analyses were performed using random effect models. The 7 included studies were of high quality (≥5 out of 7 on the adapted Newcastle-Ottawa Scale). Analgesic use in residents with and without dementia or cognitive impairment ranged from 20.2% to 61.2% and 38.8% to 79.6%, respectively. Paracetamol was the most prevalent analgesic in people with and without dementia. Residents with dementia or cognitive impairment had a significantly lower prevalence of analgesic use (odds ratio [OR] 0.576, 95% confidence interval [CI] = 0.406-0.816) and of self-reported and clinician-observed pain (OR 0.355, 95% CI = 0.278-0.454) than residents without cognitive impairment, despite a comparable prevalence of painful conditions. These findings may indicate under-reporting and under-detection of pain in persons with dementia, and subsequent suboptimal treatment.

There is uncertainty in relation to the effect of alcohol consumption on the incidence of dementia and cognitive decline. This review critically evaluated published systematic reviews on the epidemiology of alcohol consumption and the risk of dementia or cognitive decline. MEDLINE, EMBASE and PsycINFO were searched from inception to February 2014. Systematic reviews of longitudinal observational studies were considered. Two reviewers independently completed the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool to assess the quality. We identified three moderate quality systematic reviews (AMSTAR score 4-6) that included a total of 45 unique studies. Two of the systematic reviews encompassed a meta-analysis. Light to moderate drinking may decrease the risk of Alzheimer’s disease (AD) (pooled risk ratio [RR] 0.72; 95% confidence interval [CI] 0.61-0.86) and dementia (RR 0.74; 95%CI 0.61-0.91) whereas heavy to excessive drinking does not affect the risk (RR 0.92; 95%CI 0.59-1.45 and RR 1.04; 95%CI 0.69-1.56, respectively). One systematic review identified two studies that reported a link between alcohol consumption and the development of AD. No systematic review categorised former drinkers separately from lifetime abstainers in their analysis. Definitions of alcohol consumption, light to moderate drinking and heavy-excessive drinking varied and drinking patterns were not considered. Moderate quality (AMSTAR score 4-6) systematic reviews indicate that light to moderate alcohol consumption may protect against AD and dementia. However, the importance of drinking patterns and specific beverages remain unknown. There is insufficient evidence to suggest abstainers should initiate alcohol consumption to protect against dementia.

Impaired cognition has a significant impact on a person’s ability to manage their medicines. The aim of this paper is to provide a narrative review of contemporary literature on medicines management by people with dementia or cognitive impairment living in the community, methods for assessing their capacity to safely manage medicines, and strategies for supporting independent medicines management. Studies and reviews addressing medicines management by people with dementia or cognitive impairment published between 2003 and 2013 were identified via searches of Medline and other databases. The literature indicates that as cognitive impairment progresses, the ability to plan, organise, and execute medicine management tasks is impaired, leading to increased risk of unintentional non-adherence, medication errors, preventable medication-related hospital admissions and dependence on family carers or community nursing services to assist with medicines management. Impaired functional capacity may not be detected by health professionals in routine clinical encounters. Assessment of patients’ (or carers’) ability to safely manage medicines is not undertaken routinely, and when it is there is variability in the methods used. Self-report and informant report may be helpful, but can be unreliable or prone to bias. Measures of cognitive function are useful, but may lack sensitivity and specificity. Direct observation, using a structured, standardised performance-based tool, may help to determine whether a person is able to manage their medicines and identify barriers to adherence such as inability to open medicine packaging. A range of strategies have been used to support independent medicines management in people with cognitive impairment, but there is little high-quality research underpinning these strategies. Further studies are needed to develop and evaluate approaches to facilitate safe medicines management by older people with cognitive impairment and their carers.

There currently is no cure or established preventative treatment for Alzheimer's disease (AD). Considering the increasing aging population and the subsequent high prevalence of AD worldwide, identifying a cost-effective way to prevent AD is an essential unmet medical need. Relative to healthy human brain samples, postmortem AD brain samples have been shown to exhibit lower docosahexaenoic acid (DHA) levels, an essential polyunsaturated fatty acid required for normal neuronal function. However, findings from different studies are controversial and it is not clear whether this alteration in DHA brain levels is a cause or consequence of AD. Animal studies have also demonstrated that administration of DHA can alleviate the underlying pathophysiology of AD, including but not limited to amyloid pathology, tau pathology, and neuroinflammation. Moreover, DHA has been suggested to exert cognitive-enhancing effects and epidemiological studies have suggested that regular consumption of fish or omega-3 fatty acid enriched diets can attenuate the cognitive decline in AD and/or lower the risk of developing AD. However, the beneficial effects of DHA in AD have not been clearly demonstrated by current human randomised-control trials. In addition, the underlying reasons for the lower brain levels of DHA in AD remain to be fully characterised. However, given that the brain has limited capacity to produce DHA de novo and obtains DHA from the plasma, one plausible explanation for the lower brain levels of DHA in AD is reduced bloodbrain barrier (BBB) transport of this fatty acid in AD, as has been reported in one mouse model of AD. Unfortunately, the actual mechanisms governing the BBB transport of DHA in healthy conditions are not clearly understood, complicating the relationship between reduced BBB transport of DHA, attenuated DHA brain levels and AD pathology. The purpose of this review, therefore, is to summarise the findings of the biochemical, functional and epidemiological studies assessing the impact of DHA on the progression of AD, with a focus on how brain DHA levels alter in AD, the mechanisms thought to be held responsible for the apparent protective effects of DHA in AD, and the factors governing BBB transport of DHA in AD.

Tuberculosis is one of the leading causes of morbidity and mortality worldwide. Current treatment has several challenges, such as multi-drug resistance, extensively drug-resistance and HIV co-infection. Problems related to patients, treatment and health care system also contribute negatively to this panel. This review summarizes the main obstacles causing in the treatment of tuberculosis and discusses several strategies to improve the treatment.