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ABSTRACT: 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 respon-dents 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.
International Journal of Geriatric Psychiatry 01/2013; · 2.42 Impact Factor
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ABSTRACT: 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 © 2012 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry 12/2012; 27(12):1258-1266. · 2.42 Impact Factor
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ABSTRACT: β-site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of beta-amyloid peptides
(Aβ), which are proposed to drive the pathological changes found in Alzheimer’s disease (AD). Reticulon 3 (RTN3) is a negative
modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively
regulates BACE1 expression. The present study investigated whether there was any association between genetic variation in
RTN3 and PPIL2, and either risk for AD, or levels of platelet β-secretase activity, in a large Northern Irish case-control sample. Four hundred
and sixty-nine patients with a diagnosis of probable AD (NINCDS-ADRDA criteria) and 347 control individuals (MMSE>28/30)
were genotyped. SNPs in both genes were selected by downloading genotype data from the International HapMap Project (Phase
II) and tags selected using multimarker approach in Haploview, where r
2>0.8 and LOD>3.0. Non-synonymous SNPs of interest were also included. Genotyping was performed by Sequenom iPLEX and TaqMan
technologies. Alleles, genotypes and multi-marker haplotypes were tested for association with AD, and platelet β-secretase
activities were measured for a subset of individuals (n=231). Eight SNPs in RTN3 and 7 in PPIL2 were genotyped. We found no significant associations between allele, genotype or haplotype frequencies and risk of AD. Further,
there was no effect of genotype on platelet membrane β-secretase activity. We conclude that common or potentially functional
genetic variation in these BACE1 interacting proteins does not affect platelet membrane β-secretase activity or contribute
to risk of AD in this population.
NeuroMolecular Medicine 04/2012; 11(4):337-344. · 5.00 Impact Factor
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ABSTRACT: Psychotic symptoms are common in Alzheimer’s disease (AD) and have a negative impact on quality of life. It is suggested that
psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene
for the α7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association studies. Hence
we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously
described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223
(P=0.014, OR=1.63, CI=1.22–2.17) was found. This suggests that the α7 receptor may be a suitable target for the treatment
of AD with psychosis.
NeuroMolecular Medicine 04/2012; 10(4):377-384. · 5.00 Impact Factor
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ABSTRACT: Recent years have seen a growing recognition that dementia is a terminal illness and that patients with advanced dementia nearing the end of life do not currently receive adequate palliative care. However, research into palliative care for these patients has thus far been limited. Furthermore, there has been little discussion in the literature regarding medication use in patients with advanced dementia who are nearing the end of life, and discontinuation of medication has not been well studied despite its potential to reduce the burden on the patient and to improve quality of life. There is limited, and sometimes contradictory, evidence available in the literature to guide evidence-based discontinuation of drugs such as acetylcholinesterase inhibitors, antipsychotic agents, HMG-CoA reductase inhibitors (statins), antibacterials, antihypertensives, antihyperglycaemic drugs and anticoagulants. Furthermore, end-of-life care of patients with advanced dementia may be complicated by difficulties in accurately estimating life expectancy, ethical considerations regarding withholding or withdrawing treatment, and the wishes of the patient and/or their family. Significant research must be undertaken in the area of medication discontinuation in patients with advanced dementia nearing the end of life to determine how physicians currently decide whether medications should be discontinued, and also to develop the evidence base and provide guidance on systematic medication discontinuation.
Drugs & Aging 06/2010; 27(6):435-49. · 2.67 Impact Factor
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ABSTRACT: To compare the performance of patients with mild-moderate Alzheimer's disease (AD) and vascular dementia (VaD) on tests of information processing and attention.
Patients with AD (n=75) and VaD (n=46) were recruited from a memory clinic along with dementia-free participants (n=28). They underwent specific tests of attention from the Cognitive Drug Research battery, and pen and paper tests including Colour Trails A and B and Stroop. All patients had a CT brain scan that was independently scored for white-matter change/ischaemia.
Attention was impaired in both AD and VaD patients. VaD patients had more impaired choice reaction times and were less accurate on a vigilance test measuring sustained attention. Deficits in selective and divided attention occurred in both patient groups and showed the strongest correlations with Mini Mental State Examination scores.
This study demonstrates problems with the attentional network in mild-moderate AD and VaD. The authors propose that attention should be tested routinely in a memory clinic setting.
Journal of neurology, neurosurgery, and psychiatry 02/2010; 81(2):157-9. · 4.87 Impact Factor
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Archives of internal medicine 01/2010; 170(1):107. · 11.46 Impact Factor
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ABSTRACT: Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Abeta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.
Journal of Neurochemistry 02/2009; 108(2):341-9. · 4.06 Impact Factor
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ABSTRACT: Renal disease is increasingly regarded as an independent risk factor for vascular disease which in itself is believed to influence risk of AD. Alterations in amyloid homeostasis via reduced renal clearance of peripheral beta-amyloid (A|*beta*|) may represent another potential role for variation in renal function leading to increased risk of AD. We sought to examine estimates of glomerular filtration rate in AD and control groups.
AD patients were randomly recruited from the Memory Clinic of the Belfast City Hospital (n = 83). Genomic DNA was extracted from peripheral leucocytes and was genotyped for Apolipoprotein E using standard methods. Using creatinine values, age and gender, estimated Glomerular Filtration Rates (eGFR) were calculated using the isotope dilution mass spectrometry (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) Study equation (using the United Kingdom National External Quality Assessment Scheme (UKNEQAS) correction factor). IDMS eGFR values were then compared between AD and control groups.
Significant baseline differences in age, diastolic blood pressure, education level attained and APOE |*epsilon*|4 carriage were noted between cases and controls. The AD group had a significantly lower eGFR versus controls (69 vs 77 ml/min) which persisted after adjustment for possible confounders (p = 0.045).
This case-control analysis suggests that using a relatively accurate estimate of renal function, patients with AD have greater renal impairment than cognitively normal controls. This may reflect impaired renal clearance of peripheral A|*beta*| or be a marker of shared vascular processes altering cerebral and renal functioning.
International Journal of Geriatric Psychiatry 02/2009; 24(9):927-32. · 2.42 Impact Factor
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ABSTRACT: Research into the cause of Alzheimer’s disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Aβ peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane β-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane β-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y β-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane β-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.
Journal of Neurochemistry 10/2008; 108(2):341 - 349. · 4.06 Impact Factor
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ABSTRACT: The presenilins (PSs) were identified as causative genes in cases of early-onset familial Alzheimer's disease (AD) and current evidence indicates that PSs are part of the gamma-secretase complex responsible for proteolytic processing of type I membrane proteins. p75NTR, a common neurotrophin receptor, was shown to be subject to gamma-secretase processing. However, it is not clear if the p75NTR downstream signal is altered in response to gamma-secretase cleavage, and further there is a possibility that AD-related PS mutations may affect this cleavage, resulting in pathogenic alterations in signal transduction. In this study, we confirmed that p75NTR downstream signalling is altered by PS2 mutation or gamma-secretase inhibition in SHSY-5Y cells. The activity of the small GTPase RhoA is strongly affected by these treatments. This study demonstrates that gamma-secretase and PS2 play an important role in regulating neurotrophin signal transduction and either mutation of PS2 or inhibition of gamma-secretase disturbs this function.
Neurobiology of Disease 10/2007; 27(3):258-64. · 5.40 Impact Factor
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ABSTRACT: To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD).
A case-control association analysis.
Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A).
Patients with AD diagnosed according to standard criteria.
Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods.
Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype.
We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.
Sleep 09/2006; 29(8):1003-7. · 5.05 Impact Factor
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ABSTRACT: 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.
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).
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.
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.
American Journal of Geriatric Psychiatry 07/2005; 13(6):460-8. · 3.64 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) and vascular dementia (VaD) are both associated with deficits in cholinergic neurotransmission that are amenable to therapeutic intervention. The cholinesterase inhibitor, donepezil, is clinically effective in both AD and VaD. Results from a 10-study metaanalysis of donepezil (5 or 10 mg/day) in AD and a two-study combined analysis of donepezil (5 or 10 mg/day) in VaD are presented to compare patient characteristics and donepezil treatment outcomes. The analyzed studies were randomized, placebo-controlled, and of up to 24 weeks duration. In both AD and VaD, donepezil provided significant benefits compared with placebo on measures of cognition and global function. Placebo-treated AD patients showed a decline in cognition and global function, whereas placebo-treated VaD patients remained stable, suggesting treatment effects of donepezil in VaD were driven by improvement rather than stabilization or reduced decline. More VaD patients than AD patients received concomitant medications. Cardiovascular adverse events were more common in VaD than AD patients but were not increased by donepezil. In conclusion, although there are differences between AD and VaD patients in comorbid conditions and concomitant medications, donepezil is effective and well tolerated in both types of dementia.
Journal of the Neurological Sciences 04/2005; 229-230:141-6. · 2.35 Impact Factor
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ABSTRACT: 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.
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.
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.
These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.
Dementia and Geriatric Cognitive Disorders 02/2005; 19(2-3):154-7. · 2.14 Impact Factor
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ABSTRACT: 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.
Neuroscience Letters 10/2004; 368(1):33-6. · 2.11 Impact Factor
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ABSTRACT: The explanation for why some patients develop psychotic change in Alzheimer's disease (AD) is unclear. "Psychosis-modifier genes" may act in the setting of neurodegeneration to produce AD plus psychosis in a similar way to how genetic modulation during neurodevelopment leads to schizophrenia. Because there is increasing interest in the common disruption of cytokine pathways seen in both AD and schizophrenia, we tested the association between the functional interleukin-1beta -511 promoter polymorphism with delusions and hallucinations in AD. Significant associations between psychotic symptoms and the CC genotype (p = 0.001 - p = 0.043) and C allele (p = 0.014 vs p = 0.048) were found, thus confirming the previously noted increased risk in schizophrenia.
Annals of Neurology 08/2004; 56(1):121-4. · 11.09 Impact Factor
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ABSTRACT: The behavioural and psychological symptoms of dementia are common, distressing to carers, and directly linked to the requirement for institutional care. Symptoms of aggression and agitation are particularly difficult for carers to tolerate. The origin of these features is unclear although genetic and environmental modification of pre-frontal serotonergic circuitry which regulates the control of negative emotions is proposed. Following the suggestion that the A218C intronic polymorphism of the tryptophan hydroxylase gene influences aggression and anger in non-demented individuals, we tested the influence of A218C on symptoms of agitation/aggression in 396 Alzheimer's disease patients using the Neuropsychiatric Inventory. Overall, 50% of participants experienced agitation/aggression in the month prior to interview. It was observed that male patients with a history of agitation/aggression were more likely to possess C-containing genotypes (P = 0.044, OR = 1.65, CI = 0.98-2.76). We conclude that aggression in male subjects with Alzheimer's disease may be genetically linked to polymorphic variation at the tryptophan hydroxylase gene.
Neuroscience Letters 07/2004; 363(3):199-202. · 2.11 Impact Factor
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ABSTRACT: Elevated plasma homocysteine level has been associated with increased risk for cardiovascular and cerebrovascular disease. Variation in the levels of this amino acid has been shown to be due to nutritional status and methylenetetrahydrofolate reductase (MTHFR) genotype.
Under a case-control design we compared fasting levels of homocysteine and MTHFR genotypes in groups of subjects consisting of stroke, vascular dementia (VaD), and Alzheimer disease patients and normal controls from Northern Ireland.
A significant increase in plasma homocysteine was observed in all 3 disease groups compared with controls. This remained significant after allowance for confounding factors (age, sex, hypertension, cholesterol, smoking, creatinine, and nutritional measures). MTHFR genotype was not found to influence homocysteine levels, although the T allele was found to increase risk for VaD and perhaps dementia after stroke.
We report that moderately high plasma levels of homocysteine are associated with stroke, VaD, and Alzheimer disease. This is not due to vascular risk factors, nutritional status, or MTHFR genotype.
Stroke 11/2002; 33(10):2351-6. · 5.73 Impact Factor
