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Theta–gamma coupling (TGC) is a neurophysiological process that supports working memory. Working memory is associated with other clinical and biological features. The extent to which TGC is associated with these other features and whether it contributes to working memory beyond these features is unknown. Two-hundred-and-three older participants at risk for Alzheimer's dementia—98 with mild cognitive impairment (MCI), 39 with major depressive disorder (MDD) in remission, and 66 with MCI and MDD (MCI + MDD)—completed a clinical assessment, N-back-EEG, and brain MRI. Among them, 190 completed genetic testing, and 121 completed [11C] Pittsburgh Compound B ([11C] PIB) PET imaging. Hierarchical linear regressions were used to assess whether TGC is associated with demographic and clinical variables; Alzheimer's disease-related features (APOE ε4 carrier status and β-amyloid load); and structural features related to working memory. Then, linear regressions were used to assess whether TGC is associated with 2-back performance after accounting for these features. Other than age, TGC was not associated with any non-neurophysiological features. In contrast, TGC (β = 0.27; p = 0.006), age (β = − 0.29; p = 0.012), and parietal cortical thickness (β = 0.24; p = 0.020) were associated with 2-back performance. We also examined two other EEG features that are linked to working memory—theta event-related synchronization and alpha event-related desynchronization—and found them not to be associated with any feature or performance after accounting for TGC. Our findings suggest that TGC is a process that is independent of other clinical, genetic, neurochemical, and structural variables, and supports working memory in older adults at risk for dementia. [ABSTRACT FROM AUTHOR]

Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ERS) and parietal alpha event-related desynchronization (ERD) index cognitive control and interference inhibition, respectively. Relative contributions of TGC, theta ERS, and alpha ERD in relation to stimulus presentation are not characterized. Further, differential effect of normal aging on pre- or post-stimulus processes is unknown. Electroencephalography was recorded in 66 younger and 41 older healthy participants while performing 3-back working memory task. We assessed relationships between 3-back task performance and each of post-stimulus TGC, pre-stimulus parietal alpha ERD, and pre-stimulus frontal theta ERS in each age group. While older adults performed worse on 3-back task than younger adults, TGC, alpha ERD, or theta ERS did not differ between the two groups. TGC was positively associated with 3-back performance in both age groups; pre-stimulus alpha ERD was associated with performance among younger adults; and pre-stimulus theta ERS was not associated with performance in either group. Our findings suggest that both pre-stimulus interference inhibition and post-stimulus ordering of information are important for working memory in younger adults. In contrast, performance in older adults appears to depend only on post-stimulus ordering of information. These specific contributions of neurophysiological resources may explain the poorer performance of older adults and suggest different targets to enhance working memory in age groups. [ABSTRACT FROM AUTHOR]

Background: Medical cannabis use is growing among older adults. In this retrospective study, we aimed to assess the characteristics of older medical cannabis users including the indications, type and amount of cannabis used, perceived changes in symptoms after cannabis use, change in dose of concurrent medications, and adverse effects. Methods: Data were collected between October 2014 and October 2020 from patients who were consulting the Canada-wide network of clinics of a medical cannabis provider and who were willing to answer questionnaires based on their medical status. The current study included older adults (≥ 65 years) who completed questionnaires at intake and first follow-up visits. Data were summarized with descriptive statistics, which were compared between men and women with t tests or chi-squared tests. Tests of proportions assessed categorical responses for perceived effects after cannabis use. Logistic regression was used to assess trends in cannabis usage. Results: Data included that from 9766 older adult users at intake (mean ± SD age = 73.2 ± 6.8 years, females = 60.0%), among whom 4673 (females = 61.4%) returned for follow-up after 90.6 ± 58 days. The most common primary indication for which medical cannabis was sought was pain (67.7%), which was more common in women, whereas oncological and neurological conditions were more common in men. At follow-up, cannabis oil was used by 81.0% of older adults, among whom compositions containing only or mostly cannabidiol (CBD) had been used by 83.6%. Adverse effects reported by older adults at the follow-up visit included dry mouth (12.8%), drowsiness (8.6%), and dizziness (4.0%). The majority of older adults reported improvements in pain (72.7%, z = 1482.6, p < 0.0001, compared to worsening or no change), sleep (64.5%, z = 549.4, p < 0.0001), and mood (52.8%, z = 16.4, p < 0.0001), with 35.6% reporting use of a reduced dose of opioids and 19.9% a reduced dose of benzodiazepines. Interpretation: Among older adults, medical cannabis is used more often by women, with CBD-containing cannabis oils being the most commonly used. Users reported improved pain, sleep, and mood symptoms at follow-up after cannabis use. This study describes the patterns of use of medical cannabis by older adults and highlights the need for research to determine appropriate indications, precise doses of active ingredients, and short- and long-term outcomes among older adults. [ABSTRACT FROM AUTHOR]

Apathy is a highly prevalent symptom of dementia. Despite its association with faster cognitive and functional decline, decreased quality of life and increased mortality, no therapies are currently approved to treat apathy. The objective of this review was to summarize the drugs that have been studied for apathy treatment in patients with dementia (specifically Alzheimer's disease [AD], Huntington's disease [HD] and Parkinson's disease [PD] dementia; dementia with Lewy bodies [DLB]; vascular dementia [VaD]; and frontotemporal dementia [FTD]) based on their putative mechanisms of action. A search for relevant studies was performed using ClinicalTrials.gov and PubMed. Eligible studies were randomized controlled trials that were available in English and included at least one drug intervention and an apathy measure scale. A total of 52 studies that included patients with AD (n = 33 studies), PD (n = 5), HD (n = 1), DLB (n = 1), FTD (n = 3), VaD (n = 1), VaD and AD (n = 4), VaD and mixed dementia (n = 1), and AD, VaD and mixed dementia (n = 3) were eligible for inclusion. These studies showed that methylphenidate, olanzapine, cholinesterase inhibitors, choline alphoscerate, citalopram, memantine, and mibampator are the only beneficial drugs in AD-related apathy. For PD-related apathy, only methylphenidate, rotigotine and rivastigmine showed benefits. Regarding FTD- and DLB-related apathy, initial studies with agomelatine and rivastigmine showed benefits, respectively. As for HD- and only-VaD-related apathy, no drugs demonstrated benefits. With regards to mixed populations, memantine, galantamine and gingko biloba showed effects on apathy in the AD plus VaD populations and nimodipine in the VaD plus mixed dementia populations. Of the drugs with positive results, some are already prescribed to patients with dementia to target other symptoms, some have characteristics—such as medical contraindications (e.g., cardiovascular) and adverse effects (e.g., gastrointestinal disturbances)—that limit their clinical use and some require further study. Future studies should investigate apathy as a primary outcome, making use of appropriate sample sizes and study durations to ensure durability of results. There should also be a consensus on using scales with high test/retest and interrater reliabilities to limit the inconsistencies between clinical trials. In conclusion, there are currently no US FDA-approved drugs that target apathy in dementia, so there is an ongoing need for the development of such drugs. [ABSTRACT FROM AUTHOR]

Data on respiratory-related illness and respiratory syncytial virus (RSV) infection in children with a tracheostomy are sparse. We determined respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios in children with a tracheostomy following prophylaxis compared with infants' prophylaxed for standard indications (prematurity ≤ 35 weeks' gestational age, bronchopulmonary dysplasia, and significant congenital heart disease) and children with complex medical disorders. Children who received ≥ 1 injection of palivizumab were prospectively enrolled across 32 Canadian sites during the RSV season. Respiratory illness event data were collected monthly. Data were analyzed using t tests, chi-square tests, and Cox proportional hazards adjusted for confounders. A total of 23,597 infants were enrolled; 220 tracheostomy, 19,402 standard indications, 3975 complex medical disorders. Of the 220 tracheostomy infants, 30 had bronchopulmonary dysplasia, 18 were premature, 12 had congenital heart disease, and 160 had other medical complexities. RIH and RSVH incidences (tracheostomy, standard indications, complex medical disorders) were 24.5%, 6.2%, and 9.8% and 2.0%, 1.5%, and 1.8% respectively. RIH hazard was significantly higher in tracheostomy infants compared with standard indications (HR = 1.8, 95% CI 1.1–3.0, p = 0.02) but was similar between the tracheostomy and complex medical disorders groups (HR = 1.3, 95% CI 0.7–2.2, p = 0.37). RSVH hazard was also similar in tracheostomy infants relative to standard indications and complex medical disorders (both p > 0.75). Children with tracheostomies who received palivizumab had an increased RIH hazard compared with the standard indications group. Similar RSVH hazard between tracheostomy, standard indications, and complex medical disorders groups suggests that children with tracheostomies may benefit from palivizumab by reducing RSVH during the RSV season. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms associated with dementia are highly prevalent and are associated with an increased risk of institutionalization and mortality. Current pharmacological treatments for these symptoms include cholinesterase inhibitors, antipsychotics, and selective serotonin reuptake inhibitors. When used for treating behavioral and psychological symptoms associated with dementia, they are associated with limited efficacy and/or serious adverse events. As such, there has been extensive research into novel agents with varying mechanisms of action targeting behavioral and psychological symptoms associated with dementia. In this article, we present the results of a comprehensive literature search and review that evaluates current agents that have completed or are currently in clinical trials for treating behavioral and psychological symptoms associated with dementia as a primary outcome. We highlight novel agents from miscellaneous drug classes, such as dextromethorphan/quinidine, bupropion/dextromethorphan, lumateperone, deudextromethorphan/quinidine, methylphenidate and scyllo-inositol, and drugs from various therapeutic classes (including atypical antipsychotics, selective serotonin reuptake inhibitors, and cannabinoids) that have demonstrated promising results and were generally well tolerated. Future research with large appropriately powered studies using validated outcome measures for behavioral and psychological symptoms associated with dementia should be conducted to further establish the clinical utility of these agents. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study’s objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged < 2 years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ2 and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B) = 0.23 [0.11-0.49], p < 0.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; t = 2.39 [df = 7], p = 0.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (t = 3.52 [df = 15], p = 0.003) and hospital LOS (t = 2.11 [df = 52], p = 0.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = −0.454, P <0.001), TNF-α (g = −0.202, P = 0.015), IL-10 (g = −0.566, P = 0.012), and CCL-2 (g = −1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders. [ABSTRACT FROM AUTHOR]

Children aged <2 years with chronic lung disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29 weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all p < 0.0005. RIH rates were 12.2 (FY) and 18.2 (SY), and RSVH rates were 2.3 (FY) and 3.9 (SY). Cox regression showed similar hazards for both RIH (hazard ratio 0.9, 95% CI 0.6-1.6, p = 0.812) and RSVH (hazard ratio 1.1, 95% CI 0.4-2.9, p = 0.920).Conclusions: SY and FY children had similar risks for RIH and RSVH. The findings imply that SY children with CLD are correctly selected for palivizumab based on neonatal illness severity and merit prophylaxis. What is Known: • Children with chronic lung disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections. • The American Academy of Pediatrics [ 2 ] and the Canadian Paediatric Society [ 30 ] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those <32 weeks gestation or those in the first year of life who are oxygen dependent or require medical therapy for the treatment of their condition. What is New: • Children with chronic lung disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS). • CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity. [ABSTRACT FROM AUTHOR]

Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to measure the economic value of cholinesterase inhibitors when used to treat Alzheimer's disease using the willingness-to-pay (WTP) approach and the framework of cost-benefit analysis.Methods and Study Design: A cost-benefit analysis using the WTP approach was employed. The study sample consisted of 28 nonprofessional caregivers of outpatients with mild to moderate dementia from Toronto, ON, Canada. The caregivers were presented with four scenarios. In the first scenario, scenario A, a hypothetical patient with mild dementia was stabilised with a cholinesterase inhibitor. In the second scenario, scenario A with adverse effects, the above patient (A) experienced adverse effects caused by the drug. In the third scenario, scenario B, the patient exhibited behavioural symptoms in addition to mild dementia, and both were stabilised with the drug. In the fourth scenario, scenario B with adverse effects, the above patient (B) experienced adverse effects caused by the drug. The caregivers were then asked what amount they would pay, in Canadian dollars, each year to buy the medication, assuming that they were the caregivers of the patient described. A multivariate regression analysis was performed to assess the relationship between the demographic data (including the caregiver's yearly income) and the WTP. The average WTP was also predicted for the general population and the elderly population of Canada using data from Statistics Canada, and these values were compared with the cost of the medication.Study Perspective: Nonprofessional caregiver perspective. All monetary values are 1999 values unless otherwise specified.Results: The mean yearly WTP was $Can4540 (95% CI 2334-6746) for scenario A, $Can3686 (95% CI 1530-5842) for scenario A with adverse effects, $Can5003 (95% CI 2661-7345) for scenario B and $Can4486 (95% CI 2222-6750) for scenario B with adverse effects. The WTP decreased when drug adverse effects were present (significantly in scenario A; p = 0.04), but did not significantly increase when behavioural symptoms were present and stabilised. In all scenarios, caregiver yearly income was the only significant predictor of WTP, in the direction expected. For all scenarios, the calculated WTPs from the regression analysis using our sample mean, the average Canadian population data and the elderly population data were all higher than the yearly cost of the cholinesterase inhibitors, with the net benefit ranging from $Can1723 to $Can4508.Conclusions: The results of the study, from a small sample of nonprofessional caregivers, revealed that the caregivers are willing to pay more for cholinesterase inhibitors than the drugs cost, even when the adverse effects of the drugs are taken into consideration. This indicates a net benefit for cholinesterase inhibitors in the treatment of mild to moderate dementia from a consumer's point of view. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is frequently associated with neuropsychiatric symptoms (NPS) such as agitation and aggression, especially in the moderate to severe stages of the illness. The limited efficacy and high-risk profiles of current pharmacotherapies for the management of agitation and aggression in AD have driven the search for safer pharmacological alternatives. Over the past few years, there has been a growing interest in the therapeutic potential of medications that target the endocannabinoid system (ECS). The behavioural effects of ECS medications, as well as their ability to modulate neuroinflammation and oxidative stress, make targeting this system potentially relevant in AD. This article summarizes the literature to date supporting this rationale and evaluates clinical studies investigating cannabinoids for agitation and aggression in AD. Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids—dronabinol or nabilone—on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies. Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD. [ABSTRACT FROM AUTHOR]

Caregiving for patients with Alzheimer's disease (AD) is associated with negative outcomes for the caregiver such as depression, anxiety, medical ill- ness, poorer general health and mortality, which further translate into ad- verse outcomes for the patient. The burden experienced by caregivers of AD patients, both professional and informal, has been found to be positively related to the presence and severity of the patients' neuropsychiatric symptoms, also referred to as the behavioural and psychological symptoms of dementia (BPSD). As such, management of BPSD may help in alleviating caregiver burden. The purpose of this review is to summarize the current literature on the effects of pharmacological interventions for BPSD on the burden of AD patient caregivers. A literature review was conducted, using keywords related to dementia, drug treatment, caregiving and BPSD. Studies were included if they were a randomized controlled trial of a currently mar- keted drug in AD patients, and included a measure of caregiver burden and BPSD. Twenty-four articles met the eligibility criteria for this review. Cognitive enhancers (cholinesterase inhibitors, memantine) were associated with de- creased caregiver burden in some studies, though it is unclear whether the improvements were related to changes in BPSD or cognition and function. Antipsychotics have been associated with decreased caregiver burden in some studies, though variability may be related to disease severity. Other drug treat- ments, including antidepressants, have also been shown to have inconsistent effects on caregiver burden. Besides the small number of clinical trials that included a measure of caregiver burden, there is large variability in the literature due to differing conceptualizations of caregiver burden and the lack of a re- cognized gold standard for caregiving burden assessment. It is therefore difficult to draw strong conclusions about whether the pharmacological management of BPSD relieves caregiver burden. Given the importance of caregiver burden and its negative consequences for the caregiver and the patient, future clinical trials should pay more attention to this crucial outcome. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive and ultimately fatal condition that causes debilitating memory loss and extensive deterioration of cognitive and functional abilities. Currently available treatments for AD (donepezil, rivastigmine, galantamine and memantine) are symptomatic and do not decelerate or prevent the progression of the disease. These therapies demonstrate modest, but particularly consistent, benefit for cognition, global status and functional ability. The search for disease-modifying interventions has focused largely on compounds targeting the amyloid-β pathway. To date, the treatments targeting this pathway, such as tramiprosate and semagacestat, have been unsuccessful in demonstrating efficacy in clinical stages of testing. At this point, it is likely that not only amyloid-β aggregation but other possible neuronal mechanisms--such as hyperphosphorylated tau, neuro- inflammation and other processes - play important roles in the pathophysiology of this multifactorial disorder. Development of better disease models and biomarkers is essential for the advancement of knowledge of the disease mechanisms. This systematic review critically examines the efficacy and safety data for currently approved drugs and emerging treatments in AD, as well as discussing the present and future directions of innovation in this field. [ABSTRACT FROM AUTHOR]

Background: Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease (AD) with a negative impact on caregivers.Objective: The aim of the study was to determine whether changes in agitation and aggression would follow memantine treatment and, if so, be associated with changes in nursing burden in institutionalized patients with moderate to severe AD.Study Design: This was a 3-month open-label trial of memantine.Setting: The setting was two long-term care facilities.Patients: Thirty-one institutionalized patients with moderate to severe AD and significant behavioural and psychiatric symptoms were included in the study.Intervention: Memantine was titrated to a target dose of 10 mg twice daily.Main Outcome Measure: Effectiveness was assessed by the change in the Neuropsychiatric Inventory-Nursing Home (NPI-NH) agitation/aggression subscale and Clinical Global Impression of Change (CGI-C) scale using the intent-to-treat population. To establish caregiver impact, the effect on nursing burden was measured by the Modified Nursing Care Assessment Scale (primary outcome). As a secondary analysis, the caregiver distress subscale of the NPI-NH was examined, as well as changes in as required (pro re nata [prn]) psychotropic medication use.Results: Twenty-four patients completed the study. A significant decrease in agitation and aggression (F-test with 3 and 90 degrees of freedom [F(3,90)] = 3.721, p = 0.014) was demonstrated following memantine, with 48% of patients improving (either much improved or minimally improved) on the CGI-C scale. In addition, nursing burden (t-test with 30 degrees of freedom [t(30)] = 3.02, p = 0.005), caregiver distress (F(3,90) = 4.125, p = 0.009) and the use of prn psychotropics decreased following memantine treatment (Z = -1.99, p = 0.046). Fourteen patients experienced at least one adverse event during memantine treatment. The most common adverse event associated with treatment was somnolence (n = 5).Conclusion: The results of this study suggest that the decreased agitated and aggressive behaviour in institutionalized patients with moderate to severe AD following treatment with memantine was accompanied by improvements in nursing burden and decreased psychotropic use. These findings should be confirmed in a larger, controlled trial. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is associated with a substantial economic impact on patients, their caregivers and society. Due to the current rise in the aging population, the prevalence and impact of Alzheimer's disease are expected to increase greatly. The cost of caring for someone with Alzheimer's disease is magnified in the more severe stages of the disease. There are four cognitive enhancers commonly used for the treatment of Alzheimer's disease: three cholinesterase inhibitors (donepezil, rivastigmine and galantamine) and one NMDA receptor antagonist (memantine). Of these, donepezil and memantine have been approved in many countries as pharmacological treatments for moderate to severe Alzheimer's disease, while donepezil, rivastigmine and galantamine are approved treatments for mild to moderate Alzheimer's dis- ease. While cost effectiveness has been well studied in mild to moderate Alzheimer's disease, the cost-benefit information for drug therapy in moderate to severe Alzheimer's disease is less clear. This article reviews the pharmaco- economic data available on these four drugs, with a specific focus on mod- erate to severe Alzheimer's disease, including economic burden, cost drivers, clinical outcomes and pharmacoeconomic studies. A key driver of the cost of Alzheimer's disease is the severity of the disease, indicating that the ability to stabilize the disease state is a potential source of cost savings. Drug therapies that can limit increases in behavioural problems and cognitive and functional impairment, and postpone institutionalization without an increase in long- evity may serve to reduce the economic burden on Alzheimer's disease patients. The data suggest that, while the available, approved agents offer only modest improvements in clinical outcomes, they could be cost-effective treatments for moderate to severe Alzheimer's disease when viewed from the societal perspective. For memantine and donepezil, data are available that suggest that the cost of these drugs is offset by the clinical and societal benefits provided by slowing the progression of Alzheimer's disease. While there are few head-to-head comparison trials, the similarity in costs of the treatments and efficacy against placebo suggest that cost effectiveness will not be substantially different among treatments. More studies that examine longitudinal resource utilization and its relationship to drug treatment in the moderate to severe stages are needed to clarify cost benefit in this population and possibly differentiate between individual medications. [ABSTRACT FROM AUTHOR]

Recent concerns regarding the use of atypical antipsychotics when used for the treatment of neuropsychiatric symptoms in dementia have led to a flurry of studies attempting to re-evaluate their place in therapy. We critically review current evidence on the safety profiles of these agents in patients with behavioural and psychological symptoms of dementia (BPSD) and provide recommendations to guide the clinician. Potential risks with this class of medications include extrapyramidal symptoms (EPS), weight gain, diabetes mellitus, cardiac conduction abnormalities (e.g. corrected QT [QTc] interval prolongation), cerebrovascular adverse events and mortality. Compared with placebo, treatment of BPSD with atypical antipsychotics leads to little or no increase in EPS and no significant weight change. Compared with typical antipsychotics, treatment of BPSD with atypical antipsychotics leads to a reduced risk of EPS, lower incidences of tardive dyskinesias and no significant weight gain. Atypical antipsychotics have not been associated with glucose intolerance, diabetes or hyperlipidaemia in elderly dementia patients. Both typical and atypical antipsychotics have been associated with cardiac conduction abnormalities, with the magnitude of QTc prolongation being slightly smaller with atypical antipsychotics. Randomised controlled trials suggest that atypical antipsychotics are associated with an increased risk of cerebrovascular adverse events, such as stroke, and an increased mortality compared with placebo. However, it appears that typical antipsychotics have similar risks of cerebrovascular adverse events and death. An increased risk of anticholinergic adverse effects and falls must also be considered with both typical and atypical antipsychotics. In summary, atypical antipsychotics are associated with potentially serious adverse events. Before prescribing these medications in elderly dementia patients, baseline EPS, ECG abnormalities and concomitant medications should be assessed, and the presence of cardiovascular, cerebrovascular and metabolic risk factors should be taken into consideration when benefits and risks are being weighed. [ABSTRACT FROM AUTHOR]

The clinical correlates of reduced serotonin (5-HT) in Alzheimer''s disease (AD) remain unknown. The hypothesis of this study was that altered central serotonergic activity is related to aggression in AD. Twenty-two institutionalized, nondepressed elderly (12 M/10 F, mean age ± SD: 82.2 ± 6.4) with probable AD, severe cognitive impairment (MMSE = 4.1 ± 4.7) and significant behavioral disturbance (Neuropsychiatric Inventory (NPI) score &ges; 8) were studied. The prolactin (PRL) response to d,l-fenfluramine (60 mg p.o.) was used as an index of central serotonergic function. The NPI aggression score, NPI irritability score, and Behavioral Pathology in AD aggression score were positively correlated to prolactin concentrations following fenfluramine challenge (rS = .61, p = .003; rS = .53, p = .012; and rS = .47, p = .029 respectively). In addition, aggressive patients showed a greater mean PRL increase (% baseline) (215 ± 60, n = 11) than nonaggressive subjects (123 ± 54, n = 11) (p = .01, 2-tailed t-test). The change in PRL concentration depended on level of cognitive impairment (p = .0004) and the gender x aggression interaction (p = .015) with the overall regression model accounting for 74% of the variance (r = 0.86, F = 11.9, p = .0001). Female aggressive subjects with less cognitive impairment had the largest response to fenfluramine challenge. These results suggest a complex link between aggression in AD and central serotonergic dysfunction having interactions with gender and cognitive impairment. [Copyright &y& Elsevier]