Age-Associated Changes of Brain Copper, Iron, and Zinc in Alzheimer's Disease and Dementia with Lewy Bodies

Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10–16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation.

Quantitative Measurement of [Na+] and [K+] in Postmortem Human Brain Tissue Indicates Disturbances in Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Alzheimer’s disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p<0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r=0.45; p<0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p<0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97±1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r=0.46; p=0.035), and frontal tissue pH (r=0.35; p=0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology.

The barriers & solutions to providing good quality palliative care in dementia in the GP practice

BACKGROUND: Dementia is a significant worldwide health issue, however, it is often insidious in onset and difficult to diagnose, therefore GPs have expressed a limited confidence in their diagnostic skills, extending into their prognostication of the disease. As a result diagnosing the terminal phase of dementia has been identified as a significant challenge to delivering effective palliative care. Therefore, identifying the challenges faced by the GPs in this field will help to guide their training and support, and as a result could assist in the provision of sustained and effective palliative care for their dementia patients.

An exploration of nursing home managers' knowledge of and attitudes towards the management of pain in residents with dementia

Background The aims of this study were to explore the knowledge, attitudes and beliefs that nursing home managers hold with regard to the assessment and management of pain in residents with dementia and to determine how these may be affected by the demographic characteristics of the respondents.

Methods A questionnaire comprising six sections was mailed, on two occasions during March and April 2010, to 244 nursing home managers in Northern Ireland (representing 96% of the nursing homes in Northern Ireland).

Results The response rate was 39%. Nearly all respondents (96%) provided care to residents with dementia, yet only 60% of managers claimed to use pain treatment guidelines within their nursing home. Respondents demonstrated good knowledge about pain in residents with dementia and acknowledged the difficulties surrounding accurate pain assessment. Nursing home managers were uncertain about how to manage pain in residents with dementia, demonstrating similar concerns about the use of opioid analgesics to those reported in previous studies about pain in older people. Managers who had received recent training (p = 0.044) were less likely to have concerns about the use of opioid analgesia than those who had not received training. Respondents' beliefs about painkillers were largely ambivalent and were influenced by the country in which they had received their nursing education.

Conclusions The study has revealed that accurate pain assessment, training of nursing staff and a standardised approach to pain management (the use of pain management guidelines) within nursing homes all have a significant part to play in the successful management of pain in residents with dementia. Copyright (c) 2012 John Wiley & Sons, Ltd.

Community pharmacists and people with dementia: a cross-sectional survey exploring experiences, attitudes, and knowledge of pain and its management

Objectives
To explore community pharmacists' experiences with and attitudes towards people with dementia, and to determine the knowledge they have about pain and its management in this patient population. 

Methods
A questionnaire comprising five sections, including the Approaches to Dementia Questionnaire, was mailed, on two occasions, during February and March 2011, to all community pharmacies in Northern Ireland (n=530). 

Results
The response rate was 34.3%. A greater proportion of pharmacists provided pharmaceutical care to people with dementia living at home (91.2%) than those living in care homes (40.1%). Respondents most frequently encountered queries relating to starting and stopping medications, compliance with medication, and availability of formulation types. The mean total score for the Approaches to Dementia Questionnaire measure was 72.8, indicating a positive attitude towards people with dementia, and respondents demonstrated a strong person-centred approach towards this patient population. The majority of respondents recognised the difficulty of assessing pain in people with dementia; however, younger pharmacists (p=0.041) and pharmacists who provided pharmaceutical care to people with dementia (p=0.012) were more likely to be aware of the pain assessment tools for use in people with dementia. Pharmacists appeared uncertain about how to appropriately manage pain in people with dementia.

Conclusions
The study has revealed that community pharmacists often encounter people with dementia, especially those living in their own homes, and they have positive attitudes towards the patient population. However, training in the assessment and management of pain in people with dementia must be developed to further improve their knowledge in this area. 

Exploring the prevalence of and factors associated with pain: a cross-sectional study of community-dwelling people with dementia

Few pain studies have made community-dwelling people with dementia (PWD) their focus. The aim of this study was to determine the prevalence of pain among this patient population and to explore medication use. Moreover, we sought to investigate patient and caregiver variables associated with the presence of pain. Community-dwelling PWD and their caregivers were recruited between May 2009 and July 2012 from outpatient memory clinics in Northern Ireland to take part in a face-to-face structured interview with a researcher. Patients' cognitive status and presence of depression were established. A full medication history was taken. Both patients and caregivers were asked to rate patients' pain, at the time of the interview and on an average day, using a 7-point verbal descriptor scale. From the 206 patients who were eligible to take part, 75 patient-caregiver dyads participated in the study (participation rate = 36.4%). The majority of patients (92.0%) had dementia classed as mild or moderate. Pain was commonly reported among the sample, with 57.3% of patients and 70.7% of caregivers reporting patient pain on an average day. Significant differences were found between patients' and caregivers' reports of pain. Two-fifths of patients (40.0%) were prescribed analgesia. Antipsychotic, hypnotic and anxiolytic drug use was low, whereas antidepressant drugs were prescribed more commonly. Presence of pain was unaffected by dementia severity; however, the use of prescribed analgesic medication was a significant predictor of the presence of pain in these patients, whether reported by the patient or their caregiver 'right now' or 'on an average day' (P < 0.001). Patient and caregiver recruitment was challenging, and remains a barrier to research in this area in the future.

Pharmacological interventions for dementia in people with Down Syndrome (Protocol).

Background: People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer’s disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear. Objectives: To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome. Search methods In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies. Selection criteria: Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment. Data collection and analysis Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessaryMain results Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine. Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias. Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death. For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death. Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetylL-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures. Authors’ conclusions Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.

General practitioners’ perceptions of the barriers and solutions to good quality palliative care in dementia

The general practitioner (GP) is in a pivotal position to initiate and adapt care for their patients living with dementia. This study aimed to elicit GPs' perceptions of the potential barriers and solutions to the provision of good-quality palliative care in dementia in their practices. A postal survey of GPs across Northern Ireland was conducted with open-ended items soliciting for barriers in their practices and possible solutions; 40.6% (138/340) were returned completed. Barriers to palliative care in dementia were perceived to be a dementia knowledge deficit for healthcare staff and the public, a resource shortfall within the GP practice and community, poor team coordination alongside inappropriate dementia care provision, and disagreements from and within families. These findings have significant implications for educators and clinicians as enhanced dementia education and training were highlighted as a strong agenda for GPs with the suggestions of dementia awareness programmes for the public.