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Objective Depression in later life is associated with a two-fold increased risk of dementia. It is not clear to what extent potentially modifiable risk factors account for this association.Method Older adults (age 50 + ) with objective health measures (n= 14,014) from the Canadian Longitudinal Study on Aging were followed for a mean duration of 35 months. Linear regression analyses were used to determine if clinically significant depression (Centre for Epidemiologic Studies Depression scale score (CESD) ≥ 10) was associated with global cognitive decline, assessed with a neuropsychological battery during follow-up, and if modifiable risk factors mediated this association.Results Depression was associated with an excess of risk factors for cognitive decline including: vascular disease, hypertension, diabetes, apnoea during sleep, higher body mass index, smoking, physical inactivity and lack of social participation. In regression analyses depression remained independently associated with cognitive decline over time (beta −0.060, P= 0.038) as did cerebrovascular disease (beta −0.197, P< 0.001), HbA1C (beta −0.059, P< 0.001), visual impairment (beta −0.070, P= 0.007), hearing impairment (beta −0.098, P< 0.001) and physical inactivity (beta −0.075, P= 0.014). In mediation analyses, we found that cerebrovascular disease (z= −3.525, P< 0.001), HbA1C (z= −4.976, P< 0.001) and physical inactivity (z= −3.998, P< 0.001) partially mediated the association between depression and cognitive decline.Conclusions In this large sample of Canadian older adults incorporating several objective health measures, older adults with depression were at increased risk of cognitive decline and had an excess of potentially modifiable risk factors. Clinicians should pay particular attention to control of diabetes, physical inactivity and risk factors for cerebrovascular disease in older adults presenting with depression as they can contribute to accelerated cognitive decline and may be addressed during routine clinical care.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in dementia-free adults aged 60–64 years from the UK Biobank. We then estimated associations between these profiles with incident dementia, cognition, and neuroimaging outcomes, and explored the differences across profiles in the effects of a polygenic risk score for Alzheimer’s disease on outcomes. In 55,333 males and 63,063 females, three sex-specific latent profiles were identified: cardiometabolic risk, substance use-related risk, and low risk. The cardiometabolic risk profile in both males and females was associated with greater incidence of all-cause dementia (male: OR [95% CI] = 2.33 [2.03, 2.66]; female: OR [95% CI] = 1.44 [1.24, 1.68]), poorer cognitive performance, greater brain atrophy, and greater white matter hyperintensity volume compared to the low risk profile. The substance use-related risk profile in males was associated with poorer cognitive performance and greater white matter hyperintensities compared to the low risk profile, but no difference in all-cause dementia incidence was observed (OR [95% CI] = 1.00 [0.95, 1.06]). In females, the substance use-related risk profile demonstrated increased dementia incidence (OR [95% CI] = 1.58 [1.57, 1.58]) and greater brain atrophy but smaller white matter hyperintensity volume compared to the low risk profile. The polygenic risk score had larger effects among females, and differentially influenced outcomes across profiles; for instance, there were larger effects of the polygenic risk score on atrophy in the cardiometabolic profile vs. the low risk profile among males, and larger effects of the polygenic risk score on loss of white matter integrity in the cardiometabolic profile vs. the low risk profile among females. These results reveal three modifiable dementia risk profiles, their unique cognitive/neuroimaging outcomes, and their interactions with genetic risk for Alzheimer’s disease. These differences highlight the need to consider population heterogeneity in risk prediction tools and in planning personalized prevention strategies.

The purpose of this study was to investigate relationships between depressive symptoms, functional disability, and physical activity over time in community-dwelling older adults. The Religious Order Study and Rush Memory and Aging Project are longitudinal cohort studies based in the United States which began recruitment in 1994 and 1997, respectively. This analysis included 1611 participants (27.4% male, 92.9% White, 74.7% cognitively normal) who were included at age 80 and followed until age 90. Depressive symptoms were assessed using the modified Center for Epidemiologic Studies Depression scale. Functional disability was assessed using the Instrumental Activities of Daily Living (IADL) scale. Physical activity was self-reported hours of weekly exercise. Reciprocal temporal relationships between these variables were investigated using a random intercept cross-lagged panel model, which decomposes observed variables into stable between-person (‘trait’) and variable within-person (‘state’) components to estimate the directional effects between variables over time. Traits for depressive symptoms, IADL disability, and physical activity were correlated. IADL disability showed autoregressive effects; disability starting at age 82 strongly predicted subsequent disability. Consistent autoregressive effects were not observed for depressive symptoms nor physical activity. Several small cross-lagged effects between states were observed for IADL disability and physical activity, as well as for IADL disability and depressive symptoms. There were no direct effects between depressive symptoms and physical activity, but several paths through IADL disability were observed between ages 82 and 88. Functional disability played an important role in octogenarians, highlighting the importance of maintaining functional independence later in life.

ABSTRACTIntroductionAt present, no pharmacological interventions have been approved for the treatment of agitation in Alzheimer’s disease (AD), an important neuropsychiatric symptom that has been linked to increased mortality and greater caregiver burden. Antipsychotics offer some benefit, but increase the risk of adverse events such as falls, extrapyramidal symptoms, stroke, and mortality. Over the past 10 years, several new and repurposed medications have shown promise for treating AD-associated agitation.Areas coveredWe review the risks and benefits of emerging therapies for agitation in AD, which include newer atypical antipsychotics, selective serotonin reuptake inhibitors, cannabinoids, and dextromethorphan combination products. Other drugs such as mirtazapine, prazosin, and lithium are also discussed. Clinicaltrials.gov, PubMed/MEDLINE, EMBASE and Cochrane Central databases were searched for relevant studies from 1 January 2012 to 1 May 2022.Expert opinionAt the present time, there are no pharmacological interventions for the treatment of agitation in AD whose benefits clearly outweigh their potential safety concerns. Therefore, management of agitation in AD should primarily be based on non-pharmacological approaches. When medications are considered necessary, they should only be initiated with the caregiver’s appreciation of their risks and benefits and with careful and ongoing assessment of their safety.

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.

IMPORTANCE: Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality. OBJECTIVE: To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and/or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included. INTERVENTIONS: Ten milligrams of methylphenidate, twice daily, vs matching placebo. MAIN OUTCOMES AND MEASURES: The coprimary outcomes included (1) change from baseline to 6 months in the NPI apathy subscale or (2) improved rating on the Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change. Other outcomes include safety, change in cognition, and quality of life. RESULTS: Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, −1.25; 95% CI, −2.03 to −0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). The difference in mean change from baseline to 6 months estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups. Of the 17 serious adverse events that occurred during the study, none were related to the study drug. No significant differences in the safety profile were noted between treatment groups. CONCLUSIONS AND RELEVANCE: This study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02346201

•This paper investigates the risk of developing Alzheimer's disease (AD) in 4,932 patients with mild cognitive impairment (MCI) who have apathy, depression, both apathy and depression, or no neuropsychiatric symptoms•MCI patients who had both apathy and depression had the greatest risk of developing AD compared to MCI patients with no neuropsychiatric symptoms.•Future studies should determine whether interventions targeting apathy and depression, can reduce risk of developing AD.

•What is the primary question addressed by this study?What are the cognitive profiles of older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI)? How do these profiles differ in terms of clinical, demographic, and brain structure features?•What is the main finding of this study?Using latent profile analysis, we identified three cognitive profiles, with differences in cognition, physical health, education, and brain structure.•What is the meaning of the finding?Older patients with rMDD can be grouped cross-sectionally based on distinct data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI.

•What is the primary question addressed by this study?—Methylphenidate treatment has shown encouraging results in initial trials of apathy in Alzheimer's disease; however, its neurobiologic rationale remains unclear.•What is the main finding of this study?—We propose that the degeneration of the prefrontal cortex in Alzheimer's disease produces symptoms of apathy. We further propose that methylphenidate treatment may ameliorate those symptoms by boosting norepinephrine and dopamine actions in prefrontal-striatal-thalamocortical circuits.•What is the meaning of the finding?—Understanding the neuronal circuits subserving motivated behavior and their reliance on catecholamine actions provides a rationale for methylphenidate in the treatment of apathy in patients with Alzheimer's disease.

•This study operationalized the diagnostic criteria for apathy (DCA) into a clinical rated questionnaire and validated it against the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale; it also compared the DCA and NPI-apathy subscale to the Dementia Apathy Interview Rating (DAIR) scale.•The NPI apathy subscale selects patients likely to meet DCA. The DCA was highly concordant with other measures used for the assessment of apathy.•The strong concordance between the DCA, NPI-apathy, and DAIR suggests that these instruments are measuring a similar conceptualization of apathy.

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•We examined the efficacy and safety of nabilone as a treatment for agitation in patients with moderate-to-severe Alzheimer's disease.•Nabilone was shown to improve agitation, overall behavior, and caregiver distress compared to placebo. While sedation was greater in nabilone treatment group, there were no between-group differences in treatment-limiting sedation.•A larger/longer trial is needed to confirm the safety and efficacy of nabilone for agitation.

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Guidelines that physicians use to assess fitness to drive for dementia are limited in their currency, applicability, and rigor of development. Therefore, we performed a systematic review to determine the risk of motor vehicle collisions (MVCs) or driving impairment caused by dementia, in order to update international guidelines on driving with dementia. Seven literature databases (MEDLINE, CINAHL, Embase, etc.) were searched for all research studies published after 2004 containing participants with mild, moderate, or severe dementia. From the retrieved 12,860 search results, we included nine studies in this analysis, involving 378 participants with dementia and 416 healthy controls. Two studies reported on self-/informant-reported MVC risk, one revealing a four-fold increase in MVCs per 1,000 miles driven per week in 3 years prior, and the other showing no statistically significant increase over the same time span. We found medium to large effects of dementia on driving abilities in six of the seven recent studies that examined driving impairment. We also found that persons with dementia were much more likely to fail a road test than healthy controls (RR: 10.77, 95% CI: 3.00–38.62, z = 3.65, p < 0.001), with no significant heterogeneity (χ2 = 1.50, p = 0.68, I2 = 0%) in a pooled analysis of four studies. Although the limited data regarding MVCs are equivocal, even mild stages of dementia place patients at a substantially higher risk of failing a performance-based road test and of demonstrating impaired driving abilities on the road.

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under-recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.

ObjectivesIncreasing evidence suggests that inflammation is involved in Alzheimer’s disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers in patients with AD compared with healthy controls (HC).MethodsOriginal reports containing measurements of peripheral inflammatory markers in AD patients and HC were included for meta-analysis. Standardised mean differences were calculated using a random effects model. Meta-regression and exploration of heterogeneity was performed using publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum measurements and immunoassay type.ResultsA total of 175 studies were combined to review 51 analytes in 13 344 AD and 12 912 HC patients. Elevated peripheral interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 and 2, α1-antichymotrypsin and decreased IL-1 receptor antagonist and leptin were found in patients with AD compared with HC. IL-6 levels were inversely correlated with mean MMSE scores.ConclusionsThese findings suggest that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment. Further studies are needed to determine the clinical utility of these markers.

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•What is the primary question addressed by this study?—The question addressed by the study must limited to only one sentence.•Do clinical characteristics of participants in the ADMET 2 trial predict better response to methylphenidate for the treatment of apathy in Alzheimer's Disease?•What is the main finding of this study?—The finding must be limited to two sentences.•Participants without anxiety or agitation, who were younger, taking a cholinesterase inhibitor, with 73-80 mmHg diastolic blood pressure, having low functional capacity, were found to respond better to methylphenidate. Combining these characteristics in a multivariate model provided individualized prediction of treatment response.•What is the meaning of the finding?—The meaning of the finding must be limited to one sentence•These clinical characteristics may affect the efficacy of methylphenidate in treating apathy, and may help clinicians identify patients most likely to respond to treatment.

This trial investigated the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment for improving depressive symptoms and cognitive performance in patients with coronary artery disease (CAD) participating in cardiac rehabilitation. Patients with CAD aged 45 to 80 years were randomized to receive either 1.9-g/d n-3 PUFA treatment or placebo for 12 weeks. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D, primary outcome) and the Beck Depression Inventory II (BDI-II). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,criteria were used to identify a depressive episode at baseline. Cognitive performance was measured using a standardized battery for vascular cognitive impairment. In 92 patients (age, 61.7 ± 8.7 y; 76% male, 40% depressed; HAM-D, 6.9 ± 5.9; BDI-II, 12.3 ± 10.9; n = 45 n-3 PUFA, n = 47 placebo), depression decreased (HAM-D, F3,91= 2.71 and P= 0.049; BDI-II, F3,91= 6.24 and P< 0.01), and cognitive performance improved (attention/processing speed, F1,91= 5.57, P= 0.02; executive function, F1,91= 14.64, P< 0.01; visuospatial memory, F1,91= 4.01, P= 0.04) over cardiac rehabilitation. Omega-3 PUFA treatment increased plasma eicosapentaenoic acid (F1,29= 33.29, P< 0.01) and docosahexaenoic acid (F1,29= 15.29, P< 0.01) concentrations but did not reduce HAM-D (F3,91= 1.59, P= 0.20) or BDI-II (F3,91= 0.46, P= 0.50) scores compared with placebo. Treatment did not improve cognitive performance; however, n-3 PUFAs significantly increased verbal memory compared with placebo in a subgroup of nondepressed patients (F1,54= 4.16, P= 0.04). This trial suggests that n-3 PUFAs do not improve depressive and associated cognitive symptoms in those with CAD. The possible benefits of n-3 PUFAs for verbal memory may warrant investigation in well-powered studies.

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Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. Although cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study was to determine if WM microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD.

Objective: To determine risk factors for clinically significant progression during 12 months in patients with mild-to-moderate Alzheimer disease.Method: Community-dwelling patients with mild-to-moderate Alzheimer disease were enrolled in a 3–year prospective study, the Canadian Outcomes Study in Dementia (commonly referred to as COSID), at 32 Canadian sites. Assessments included the Global Deterioration Scale (GDS) for disease severity, the Mini-Mental State Examination (MMSE) for cognition, the Functional Autonomy Measurement System (SMAF) for daily functioning, and the NeuroPsychiatric Inventory (NPI) for behaviour, measured at baseline and at 12 months. Logistic regression identified factors associated with GDS decline, and subsequent stepwise regression identified key independent predictors. Area under the curve (AUC) was then calculated for the model.Results: Among 488 patients (mean age 76.5 years [SD 6.4], MMSE 22.1 [SD4.6], 44.1% male), 225 (46%) showed GDS decline. After adjusting for age, baseline risk factors for deterioration included the following: poorer cognition (lower MMSE score, OR 0.55; 95% CI 0.4 to 0.72 per 5 points, P= 0.001), greater dependence (lower SMAF, OR 0.72; 95% CI 0.63 to 0.83 per 5 points, P= 0.001), and more neuropsychiatric symptoms (higher NPI, OR 1.11; 95% CI 1.02 to 1.2 per 5 points, P= 0.02), with a protective effect of male sex (OR 0.59; 95% CI 0.39 to 0.9, P= 0.02), and higher (worse) GDS score (very mild, compared with mild OR 0.25; 95% CI 0.09 to 0.70, P= 0.01; compared with moderate, OR 0.08; 95% CI 0.03 to 0.23, P< 0.001; compared with moderately severe, OR 0.03; 95% CI 0.01 to 0.11, P< 0.001). The AUC was 73% (P< 0.001) (sensitivity 90% and specificity 33%).Conclusion: The progression of Alzheimer disease in Canada can be predicted using readily available clinical information.

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Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children.

Research on efficacious treatments for apathy in Alzheimer disease has been hindered by a lack of consensus diagnosis, difficulties in measurement, and studies with small sample sizes.

Cognitive dysfunction affects 40–65% of multiple sclerosis (MS) patients. To date, conventional paper and pencil neuropsychological testing has been the method of choice for detecting deficits. However, the expense and lack of access to these tests make it difficult for many patients to obtain an assessment. With the introduction of computerized cognitive testing, certain barriers to assessment can be reduced. This paper critically reviews the currently available computerized batteries, including the Automated Neuropsychology Assessment Matrix (ANAM), the Mindstreams Computerized Cognitive Battery (MCCB), the Amsterdam Neuropsychological Tasks (ANT), the Cognitive Stability Index (CSI), and the Cognitive Drug Research (CDR) battery. Recent developments in this field show promise, although further research is required before this approach can be more widely implemented.

To assess cognitive performance as a predictor of noncompletion of cardiac rehabilitation (CR) using a standardized verbal memory test.

Palivizumab is indicated for respiratory syncytial virus (RSV) prophylaxis in high-risk children. However, relatively little is known about the current use, compliance, and outcomes associated with this medication.

Objectives: To characterize the cost of caring for an outpatient in Canada with Alzheimer disease (AD) based on disease severity, and to describe how costs change with increases in disease severity.Method: Community-dwelling patients with mild-to-moderate AD were enrolled in a 3-year, naturalistic, observational study. Assessments included cognition (Mini Mental Status Examination), global ratings (Global Deterioration Scale [GDS]), and daily function (Functional Autonomy Measurement System) as part of the Canadian Outcomes Study in Dementia. Direct (medical and nonmedical) and indirect costs were collected using resource use questionnaires. Costs at baseline were compared with costs at follow-up and correlated with disease severity.Results: Total costs associated with treating AD were significantly higher with greater disease severity. The mean total cost to treat patients with very mild AD (GDS = 2) was $367 per month, compared with $4063 per month for patients with severe or very severe AD (GDS = 6). From baseline to follow-up, the greatest changes in cost were observed in the group of patients with the most severe AD as measured by all scales. The largest component of total cost was indirect costs at most severity levels, though medication costs contributed the most in patients with very mild AD. Significant independent contributors to cost were being female, having more impaired activities of daily living, and exhibiting more neuropsychiatric symptoms.Conclusions: Costs for treating a patient with AD were strongly associated with disease severity, even though none of the patients were institutionalized. Delaying the progression of AD may reduce indirect costs and burden to caregivers.

AbstractObjective:Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks’ gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.Methods:New costs (CAN) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.Results:Incremental cost-effectiveness ratios (ICERs) rose by 742, going from 30,618/QALY to 31,360/QALY. ICER changes increased from a range of 801,297 to 820,701 for infants with zero risk factors to a decrease from 808 to 192 for infants with four or more risk factors.Conclusions:Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks’ GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.Limitations:There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.

AbstractObjective:Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The objective was to systematically examine the cost effectiveness of palivizumab in defined infant groups and identify important cost and outcome determinants.Methods:Literature searches of MedLine, the Cost-Effectiveness Analysis registry and the UK NHS Economic Evaluation Database (NHS EED) were conducted to identify economic evaluations of palivizumab compared to no prophylactic treatment for RSV prevention in any infant population. Study quality was evaluated using Quality of Health Economic Studies (QHES) criteria and results converted to 2009 CAN for comparison.Results:A total of 23 articles meeting inclusion criteria were identified, including 11 cost-utility analyses (CUAs) and 12 cost-effectiveness analyses (CEAs). Quality of individual analyses was fairly high (range 60–100, median 86). Results ranged from cost dominance for prophylaxis to 3,365,769/QALY depending on population, outcome measures, and input parameters. Base-case and sensitivity-analysis mortality rates varied between studies and influenced results.Conclusions:RSV prophylaxis with palivizumab is cost effective in specific groups of high-risk infants, especially those with multiple environmental risk factors. Cost-effectiveness estimates vary between populations and settings and are more positive in those at highest risk for RSV hospitalization.Limitations:Direct comparison of the published reports was limited by restriction to English language articles and the varied methodologies, input measures, and populations across the studies reviewed. Although reported currencies were converted to a common unit for comparison, this does not completely account for monetary and inflation differences.

Objective: Depression occurs in 18% to 45% of patients with coronary artery disease (CAD) where it is associated with an increased risk of acute coronary events and mortality. Our objective was to quantitatively summarize the data on the efficacy and tolerability of antidepressant (AD) treatment for depression in CAD.Methods: We performed a meta-analysis of randomized, placebo-controlled, double-blind trials with a database search of the English literature (to March 2008) and manual search of references.Results: Four clinical trials with ADs (mirtazapine, citalopram, fluoxetine, and sertraline) of a 9- to 24-week duration involving 798 subjects (402 ADs, 396 placebo) with documented CAD and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for depression were included. ADs were superior to placebo for decreasing Hamilton Depression Rating Scale (HDRS) scores (402 ADs, 396 placebo; weighted mean difference 1.41, 95% CI 0.53 to 2.29, P= 0.002) and Beck Depression Inventory (BDI) scores (373 ADs, 369 placebo; weighted mean difference 2.27, 95% CI 0.60 to 3.94, P= 0.008). The proportion of patients (216 ADs, 213 placebo) who responded (a 50% or more reduction in HDRS scores, OR 1.72, 95% CI 1.17 to 2.54) and remitted (HDRS of 8 or less at final assessment, OR 1.80, 95% CI 1.18 to 2.74), were also significantly higher with AD, compared with placebo, with no significant differences between the 2 groups for overall dropouts (OR 0.84, 95% CI 0.42 to 1.68) or dropout owing to adverse events (OR 1.30, 95% CI 0.75 to 2.25). The combined studies were homogeneous except for overall dropout rate (P= 0.01).Conclusion: Treatment with ADs for depression in CAD results in significant therapeutic effects without substantially increased rates of discontinuation.

To examine risk factors for lower respiratory tract infections (LRTI) hospital admission in the Canadian Arctic.

The objectives were to compare actual respiratory syncytial virus (RSV) hospitalization rates and costs in a cohort of Inuit infants to hypothetical palivizumab prophylaxis strategies for infants of all gestational ages in the Eastern Canadian Arctic.

AbstractIntroduction:Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation.Methods:Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU.Results:For all of Baffin Island infants (<1 year), the ICER was 39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of 152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of 24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time.Conclusions:The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit.

Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years SD, 7.8 years; Mini Mental Status Examination score, 19.9 SD, 4.7). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline Wilcoxon Z= −2.00; P= 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; χ2= 4.33, P= 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.

Objective: To systematically review published clinical trials of the pharmacotherapy of neuropsychiatric symptoms of Alzheimer disease (AD).Method: We searched MEDLINE and EMBASE for published English-language medical literature. Our review focused on randomized controlled trials (RCTs) and corresponding metaanalyses.Results: The pharmacotherapy of neuropsychiatric symptoms of AD has been studied with numerous RCTs. The largest number of studies has focused on antipsychotics. Data are of reasonably high quality and indicate that risperidone and olanzapine are more effective than placebo for institutionalized patients with severe agitation, aggression, and psychosis. The efficacy of antipsychotics is counterbalanced by safety concerns that include cerebrovascular adverse events and mortality. Cholinesterase inhibitors and memantine appear to have modest benefits for patients with mildly to moderately severe symptoms. Antidepressants are effective for treating depression in AD, but more data are required to determine the efficacy of trazodone and citalopram for agitation and aggression. Carbamazepine appears to be efficacious, although side effects and concerns about drug–drug interactions limit its use. The data do not support the use of valproate. Benzodiazepines should only be used for short-term, as-needed use. There are insufficient data on other pharmacologic interventions, such as beta blockers, buspirone, and estrogen preparations.Conclusions: Although there have been numerous well-designed studies of the pharmacotherapy of neuropsychiatric symptoms in AD, safer and more effective treatments are urgently needed.

The article presents a study on the prevalence and impact of post-stroke depression (PSD) in older people in Canada. It states that PSD is associated with higher cognitive and functional impairments, increased costs of health care, and excess mortality in the country. It mentions that standard clinical criteria can be used in diagnosis of PSD. It recommends active screening of all stroke patients for depression and aggressive treatment.

Objective: Depression in patients with Alzheimer's disease (AD) is common (15% to 63%) and is associated with significant morbidity and increased mortality. Our objective was to quantitatively summarize the data on the efficacy and safety of antidepressant treatment for depression complicating AD.Method: We performed a metaanalysis of randomized, double-blind, placebo-controlled trials of antidepressants with a database search of the English literature (up to 2006) and a manual search of references in the retrieved articles. We extracted the proportion of subjects who responded and remitted, experienced adverse events (AEs), discontinued treatment due to AEs, or discontinued treatment for any reason. Cognition scores were also extracted.Results: We included 5 studies, which involved 82 subjects treated with antidepressants and 83 subjects who received placebo treatment. Antidepressants were superior to placebo for both treatment response (odds ratio [OR] 2.32; 95% confidence interval [CI], 1.04 to 5.16) and remission of depression (OR 2.75; 95%CI, 1.13 to 6.65). There were no significant differences between the 2 groups for change in cognition (weighted mean difference –0.71, 95%CI, –3.20 to 1.79), overall dropouts (OR 0.70; 95%CI, 0.29 to 1.66) or dropout due to AEs (OR 1.41; 95%CI 0.36 to 5.54). The numbers needed to treat for one additional AD patient to respond to antidepressant treatment were 5 (95%CI, 3 to 59) and 5 (95%CI, 2 to 24) for remission of depression.Conclusions: Antidepressant treatment for depression in AD is efficacious, with rates of discontinuation that are comparable to placebo. Nonetheless, clinicians must be vigilant regarding the potential side effects of antidepressants in this population.