Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem

Multimorbidity and polypharmacy are increasingly prevalent across healthcare systems and settings as global demographic trends shift towards increased proportions of older people in populations. Numerous studies have demonstrated an association between polypharmacy and potentially inappropriate prescribing (PIP), and have reported high prevalence of PIP across settings of care in Europe and North America and, as a consequence, increased risk of adverse drug reactions, healthcare utilisation, morbidity and mortality. These studies have not focused specifically on people with dementia, despite the high risk of adverse drug reactions and PIP in this patient cohort. This narrative review considers the evidence currently available in the area, including studies examining prevalence of PIP in older people with dementia, how appropriateness of prescribing is assessed, the medications most commonly implicated, the clinical consequences, and research priorities to optimise prescribing for this vulnerable patient group. Although there has been considerable research effort to develop criteria to assess medication appropriateness in older people in recent years, the majority of tools do not focus on people with dementia. Of the limited number of tools available, most focus on the advanced stages of dementia in which life-expectancy is limited. The development of tools to assess medication appropriateness in people with mild-to-moderate dementia or across the full spectrum of disease severity represents an important gap in the research literature and is beginning to attract research interest, with recent studies considering the medication regimen as a whole, or misprescribing, overprescribing or underprescribing of certain medications/medication classes including anticholinergics, psychotropics, antibiotics and analgesics. Further work is required in development and validation of criteria to assess prescribing appropriateness in this vulnerable patient population, to determine prevalence of PIP in large cohorts of people with the full spectrum of dementia variants and severities and to examine the impact of PIP on health outcomes.

Nursing Home Care- Nursing Students as Carers discussing and addressing the negatives; a Northern Ireland Perspective

Abstract
The quality of nursing home care for some remains a significant cause of concern. This paper explores and discusses some of the significant critiques and limitations to nursing home care within the UK, particularly and including end of life care. The paper also explores some of the international literature by way of comparison.
Aim
To identify some of the characteristics contributing to the quality of holistic care within nursing homes
Methods
Two short narratives drawn from the experiences of nursing home care within Northern Ireland. The narrators (and co-authors to the paper) are first year student nurses who are also employed (part-time) as carers within nursing homes
Results
The paper identifies evidence of good nursing and care, together with evident quality in end of life care within nursing homes. The paper addresses the context of nursing home care and explores significant characteristics that reflect in the delivery of holistic care to nursing home residents, including the important role of a `culture’ of care, ongoing and specialist training( particularly and including within end of life care) and the important impact in the quality of nursing home leadership.
The paper concludes with some short recommendations to better develop practice within nursing homes

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area.

Mental Health and Morbidity of Caregivers and Co-Residents of individuals with Dementia: A Quasi-Experimental Design

Objectives: To determine if providing informal care to a co-resident with dementia symptoms places an additional risk on the likelihood of poor mental health or mortality compared to co-resident non-caregivers.
Design: A quasi-experimental design of caregiving and non-caregiving co-residents of individuals with dementia symptoms, providing a natural comparator for the additive effects of caregiving on top of living with an individual with dementia symptoms. 
Methods: Census records, providing information on household structure, intensity of caregiving, presence of dementia symptoms and self-reported mental health, were linked to mortality records over the following 33 months. Multi-level regression models were constructed to determine the risk of poor mental health and death in co-resident caregivers of individuals with dementia symptoms compared to co-resident non-caregivers, adjusting for the clustering of individuals within households.
Results: The cohort consisted of 10,982 co-residents (55.1% caregivers), with 12.1% of non-caregivers reporting poor mental health compared to 8.4% of intense caregivers (>20 hours of care per week). During follow-up the cohort experienced 560 deaths (245 to caregivers). Overall, caregiving co-residents were at no greater risk of poor mental health but had lower mortality risk than non-caregiving co-residents (ORadj=0.93, 95% CI 0.79, 1.10 and ORadj=0.67, 95% CI 0.56, 0.81, respectively); this lower mortality risk was also seen amongst the most intensive caregivers (ORadj=0.65, 95% CI 0.53, 0.79).
Conclusion: Caregiving poses no additional risk to mental health over and above the risk associated with merely living with someone with dementia, and is associated with a lower mortality risk compared to non-caregiving co-residents.

Statin withdrawal in people with dementia

Background: There are approximately 24 million people worldwide with dementia; this is likely to increase to 81 million by 2040. Dementia is a progressive condition, and usually leads to death eight to ten years after first symptoms. End-of-life care should emphasise treatments that optimise quality of life and physicians should minimise unnecessary or non-beneficial interventions. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors; they have become the cornerstone of pharmacotherapy for the management of hypercholesterolaemia but their ability to provide benefit is unclear in the last weeks or months of life. Withdrawal of statins may improve quality of life in people with advanced dementia, as they will not be subjected to unnecessary polypharmacy or side effects. However, they may help to prevent further vascular events in people of advanced age who are at high risk of such events.

Objectives: To evaluate the effects of withdrawal or continuation of statins in people with dementia on: cognitive outcomes, adverse events, behavioural and functional outcomes, mortality, quality of life, vascular morbidity, and healthcare costs.

Search methods: We searched ALOIS (medicine.ox.ac.uk/alois/), the Cochrane Dementia and Cognitive Improvement Group Specialised Register on 11 February 2016. We also ran additional searches in MEDLINE, EMBASE, PsycINFO, CINAHL, Clinical.Trials.gov and the WHO Portal/ICTRP on 11 February 2016, to ensure that the searches were as comprehensive and as up-to-date as possible.

Selection criteria: We included all randomised, controlled clinical trials with either a placebo or 'no treatment' control group. We applied no language restrictions.

Data collection and analysis: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, using standard methodological procedures expected by Cochrane. We found no studies suitable for inclusion therefore analysed no data.

Main results: The search strategy identified 28 unique references, all of which were excluded.

Authors' conclusions: We found no evidence to enable us to make an informed decision about statin withdrawal in dementia. Randomised controlled studies need to be conducted to assess cognitive and other effects of statins in participants with dementia, especially when the disease is advanced.

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD. METHODS: In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness. RESULTS: A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E. CONCLUSIONS: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

Behavioural and psychological syndromes in Alzheimer's disease

The origins of behavioural and psychological symptoms of dementia are still poorly understood. By focusing on piecemeal behaviours as opposed to more robust syndrome change valid biological correlates may be overlooked. Our understanding of BPSD via the identification of neuropsychiatric syndromes.

Psychotic symptoms in Alzheimer's disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene

It has been suggested that genetic influences unmasked during neurodevelopment to produce schizophrenia may appear throughout neurodegeneration to produce AD plus psychosis. Risk of schizophrenia and psychosis in Alzheimer's disease (AD) has been linked to polymorphic variation at the dopamine receptor DRD3 gene implying similar causative mechanisms. We tested this association in a large cohort of Alzheimer's disease patients with a diagnosis of probable AD of 3 years or more duration from the relatively genetically homogenous Northern Irish population. We assessed relationships between genotypes/alleles of the DRD3 BalI polymorphism and the presence or absence of psychotic symptoms (delusions, hallucinations) in AD patients during the month prior to interview and at any stage during the dementia. No significant associations were found when delusions and hallucinations were cross-tabulated against S and G alleles and SS, SG and GG genotypes. Logistic regression failed to detect any influence of APOE, gender, family history or prior psychiatric history. In conclusion, we were unable to confirm previously reported associations between the DRD3 BalI polymorphism and psychotic symptoms in AD.

alpha-Synuclein aggregation

Alpha-synuclein is a major component of Lewy bodies in Parkinson's disease and is found associated with several other forms of dementia. As with other neurodegenerative diseases, the ability of alpha-synuclein to aggregate and form fibrillar deposits seems central to its pathology. We have defined a sequence within the NAC region of alpha-synuclein that is necessary for aggregation. Exploitation of chemically modified analogues of this peptide may produce inhibitors of aggregation.

Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.