[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
International Psychogeriatrics 10/2014; · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. While 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 is to determine if white matter microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD.
49 CAD patients (66±7 years, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal appearing WM was quantified as fractional anisotropy (FA) using DTI in 9 bilateral and 2 inter-hemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%.
Executive function was most significantly associated with FA in the left parahippocampal cingulum (β=.471, t=3.381, df=44, p=.002) and left inferior fronto-occipital fasciculus (β=.430, t=2.984, df=44, p=.005). FA was not associated with memory in any of the WM tracts examined.
These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia.
American Journal of Geriatric Psychiatry 09/2014; · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline.
American Journal of Neuroradiology 08/2014; · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with coronary artery disease (CAD) are at risk of accelerated cognitive decline, particularly those with major depression. Mechanisms for cognitive deficits associated with CAD, and the effects of depression, remain poorly understood. However, CAD is associated with inflammatory processes that have been linked to neurodegeneration, may contribute to cognitive decline, and are elevated in depression. Platelet-activating factors (PAFs) are emerging as key lipid mediators that may be central to those processes and highly relevant to cognitive decline in CAD.
Journal of Neuroinflammation 07/2014; 11(1):119. · 4.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children with Down syndrome (DS) are at significant risk for respiratory syncytial virus (RSV) infection and related hospitalization. We compared hospitalization rates due to respiratory tract infection in children with DS aged <2 years who prospectively received palivizumab during the RSV season with a previously published, similar untreated DS birth cohort.
A total of 532 children with DS who prospectively received palivizumab were assembled from the prospective Canadian RSV Evaluation Study of Palivizumab registry between 2005 and 2012. The untreated group included 233 children with DS derived from a nationwide Dutch birth cohort from 2003 to 2005. Events during the RSV seasons were counted. Poisson regression analysis was performed to compare incidence rate ratios (95% confidence intervals [CIs]) between groups while controlling for observation length and known risk factors for severe RSV infection.
In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects than in palivizumab recipients (incidence rate ratio 3.63; 95% CI, 1.52-8.67). The adjusted risk of hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11; 95% CI, 0.80-1.55).
These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in children with DS during the first 2 years of life. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population.
[Show abstract][Hide abstract] ABSTRACT: Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation.
CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO2Peak) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO2Peak and age as explanatory variables.
In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO2Peak. These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO2Peak increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p<0.0001). Baseline CBF in the left post-central gyrus and baseline GM density in the right putamen predicted greater change in VO2Peak.
Perfusion and GM density were associated with fitness at baseline and with greater fitness gains with exercise. This study identifies new neurobiological correlates of fitness and demonstrates the utility of multi-modal MRI to evaluate the effects of exercise in CAD patients.
PLoS ONE 03/2014; 9(3):e91251. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer's disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort.
A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE).
At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function.
The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system.
Alzheimer's Research and Therapy 01/2014; 6(4):48. · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.
BioMed Research International 01/2014; 2014:245210. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.
Neuropsychiatric Disease and Treatment 01/2014; 10:1827-35. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease (CAD) is associated with verbal memory decline, although deterioration may be mitigated in individuals undertaking exercise interventions. Ceramide sphingolipids, suggested to play a role in pathological neurodegeneration, have been associated with the development and progression of CAD but their relationship with cognitive response to exercise has not been assessed. In this study, concentrations of very long chain ceramides (C22:0 and C24:0) were assessed as predictors of changes in verbal memory performance over 1 year in subjects with CAD undertaking cardiac rehabilitation (CR).
Verbal memory was measured using the California Verbal Learning Test 2nd Ed. (CVLT-II), from which Z-scores were calculated based on age, gender and education matched norms. Baseline plasma C22:0 and C24:0 ceramide concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Repeated measures general linear models were used to determine the association between baseline plasma ceramides and the change in verbal memory performance over 1 year of CR controlling for age and body mass index (BMI).
In patients with CAD (n = 33, mean age = 62 +/- 9 years, 84.8% male, years of education = 17 +/- 3 years), higher baseline plasma C22:0 (F1, 29 = 5.30, p = 0.03) and C24:0 (F1, 29 = 4.04, p = 0.05) concentrations significantly predicted less improvement in verbal memory performance over 1 year of CR controlling for age and BMI.
Plasma ceramide concentrations should be further examined as potential predictors of cognitive response to exercise and worse cognitive outcomes in patients with CAD.Trial registration: NCT01625754.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to determine whether the Quality of Life in Late-Stage Dementia (QUALID) scale is responsive to changes in behaviour due to therapeutic intervention.
31 long-term care residents with moderate to severe AD and agitation/aggression entered a three-month, open-label trial of memantine 10 mg BID. The relationships between the QUALID and BPSD, global improvement, and cognition at baseline and endpoint, as well as the changes in these scales as a result of treatment, were examined.
Despite a significant improvement in agitation and aggression (NPI agitation, F3,90 = 3.721, p =.014; CMAI total, F3,90 = 6.301, p =.001) and overall behaviour (NPI total, F3,90 = 4.035, p =.010), there was no significant change in QUALID score (t30 = -0.278, p =.783). The QUALID was correlated with NPI at baseline (τ = 0.270, p =.037) and endpoint (τ = 0.404, p =.002), but change scores were not correlated (τ = 0.107, p =.412).
While the QUALID correlates with behavioural measures at single time points, it does not appear to correlate with changes longitudinally associated with treatment.
Canadian geriatrics journal : CGJ. 12/2013; 16(4):180-185.
[Show abstract][Hide abstract] ABSTRACT: To determine predictors of time to readmission to a general psychiatry inpatient unit.
Data from the Minimum Data Set-Mental Health (MDS-MH), a standardized assessment used to collect demographic and clinical information, were retrospectively reviewed from April 2006 through October 2008. A total of 758 patients were eligible for the study. A set of clinically relevant predictors was generated based on a literature review. A Cox regression model was applied to determine which variables were most predictive of shorter time to readmission, and their respective hazard ratios (HR).
Covariates that were significantly associated with readmission (HR [95% CI]) included receiving a pass (3.48 [2.33, 5.17], p≤0.0005), 1-2 psychiatric admissions in the past two years (15.63 [7.50, 32.55], p≤0.0005), and more than 3 psychiatric admissions in the past two years (24.15 [11.58, 50.36], p≤0.0005). Post hoc analysis indicated that those issued passes were more commonly male (57.1% vs. 43.9%, p=0.03), with a longer length of stay (25.4±21.2days vs. 18.7±21.1days, p=0.008), and higher GAF score (62.8±11.1 vs. 57.8±13.9, p=0.003), but were otherwise similar.
The factors that were associated with reduced time to readmission were a history of previous admissions and receipt of a pass prior to discharge. These results suggest that while physicians may be able to identify patients at high risk of early readmission, issuing a pass may not fully mitigate this risk. There is a need for critical research evaluating the potential benefits of passes.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Background: Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses. Methods: MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale - Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6-DS baseline)) - (placebo (DS week 6-DS baseline)). Results: In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06-1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09-1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment. Conclusion: These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.
International Psychogeriatrics 10/2013; · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cognitive function is a significant determinant of overall quality of life in patients with coronary artery disease. Medications prescribed to control vascular risk factors often have anticholinergic effects, which can cause central side effects and affect cognitive function.
This cross-sectional study aimed to identify cognitive deficits associated with the use of anticholinergic medications in patients with coronary artery disease.
Demographics, medications, and vascular risk factors were assessed for each patient by interview and chart review. Anticholinergic burden was estimated using the anticholinergic cognitive burden scale. Cognition was assessed objectively using a battery of neuropsychologic tests, including the California Verbal Learning Test second edition, Revised Brief Visuospatial Memory Test, Stroop test, Trail-Making Test Parts A and B, Digit-Symbol Coding, FAS test, and animal naming.
Patients with coronary artery disease (mean ± standard deviation age 64.2 ± 9.1, 15.3% female) presented with 2.6 ± 1.4 vascular risk factors and were using 5.1 ± 1.8 medications. Scores on the anticholinergic cognitive burden scale were associated with poorer performance on the Trail-Making Test Part A (β = 0.280, p = 0.002), Trail-Making Test Part B (β = 0.256, p = 0.004), and animal naming (β = -0.212; p = 0.015) tasks in models controlling for age, gender, years of education, number of vascular risk factors and total medications. Beta-blockers frequently prescribed in this population (i.e., metoprolol and atenolol) accounted for a large proportion of the total anticholinergic cognitive burden score, and their use was independently associated with poorer cognitive performance in a post hoc model including the anticholinergic estimate.
Anticholinergic exposure was associated with poorer performance on tests of attention, speed, and executive function in patients with coronary artery disease.
[Show abstract][Hide abstract] ABSTRACT: Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children.
CARESS is a prospective registry of children who received ≥1 dose of palivizumab during the 2006-2012 RSV seasons across 32 sites in Canada. The objective was to compare respiratory illness (RIH) and RSV hospitalization (RSVH) hazard ratios in DS children aged <2 years who received palivizumab versus children who received prophylaxis for standard indications (SI) and for other medical illnesses (MI).
13,310 children were enrolled; DS (600; 4.5%), SI (11,081; 83.3%) and MI (1629, 12.2%), with DS children increasing over the duration from 0.1% (2006) to 4.5% (2012). Participants were significantly different in mean birth weight, gestational and enrollment age and risk factors. Children in each group received an average of 4.3 ± 1.4 (DS), 4.1 ± 1.6 (SI) and 4.5 ± 1.4 (MI) palivizumab injections per RSV season, with DS differing significantly from SI (F[2,13307]=43.6, p=0.01) but not MI (F[2,13307]=43.6, p=0.07). Compliance rates were similar across the groups. A significantly greater proportion of SI children had RIHs compared to DS (HR: 0.64 [0.48-0.84] p=0.001) but MI did not. RSVH incidence rates were: 1.53%, 1.45%, and 2.27% for DS, SI and MI respectively. Neither group nor compliance affected time to RSVH.
The proportion of DS children who received palivizumab in CARESS has increased almost 45-fold. RSVH rates were low in DS following prophylaxis and hazards were similar to those found in SI and MI.
The Pediatric Infectious Disease Journal 08/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Apathy in Dementia Methylphenidate Trial (ADMET).
Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety.
60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was -1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group.
Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. Trial Registration: ClinicalTrials.gov identifier: NCT01117181.
The Journal of Clinical Psychiatry 08/2013; 74(8):810-6. · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Apathy is one of the most frequent symptoms of dementia, still needing better measurement methods. The objective of this study was to validate a new scale for apathy in institutionalized persons with dementia (APADEM-NH).
The scale includes 26 items distributed in three dimensions: Deficit of Thinking and Self-Generated behaviors (DT): 13 items, Emotional Blunting (EB): 7 items, and Cognitive Inertia (CI): 6 items. The sample included 100 institutionalized patients (90% female) with probable Alzheimer disease (AD) (57%), possible AD (13%), AD + cerebral vascular disease (17%), Lewy body dementia (11%), and Parkinson associated to dementia (2%), covering all stages of dementia severity according to the Global Deterioration Scale and Clinical Dementia Rating. Additional assessments were the Apathy Inventory, Neuropsychiatric Inventory, Cornell Scale for Depression, and the tested scale. Re-test and inter-rater reliability were carried out in 50 patients.
All subscales lacked relevant floor and ceiling effects (<15%). Internal consistency for each dimension was (Cronbach's α): DT = 0.88, EB = 0.83, CI = 0.88; item-total correlations were >0.40; and item homogeneity 0.36-0.51. Test-retest reliability for the items was kW = 0.48-0.92; for the subscales, intraclass correlation coefficient (ICC) = 0.80-0.88; and for the total score, ICC = 0.90. Inter-rater reliability reached kW values of 0.84-1.00; subscales ICC, 0.97-0.99, and total score ICC, 0.99. Standard error of measurement for total score was 6.41 and internal validity ranged from rS = 0.69-0.80.
APADEM-NH proved to be feasible, reliable, and valid for apathy assessment in institutionalized patients suffering mild to severe dementia, discerning well between apathy and depression.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2013; · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While there have been no new medications approved for the treatment of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) reviewed and updated the clinical practice guidelines on the pharmacological management of dementia that were published previously.
This review focused on the literature for the pharmacological treatment of dementia based on studies published since the third CCCDTD in 2006. A literature search of English-language medical databases was preformed for studies pertaining to the pharmacological treatment of AD and other dementias that examined the management of cognitive and functional impairment, as well as neuropsychiatric symptoms. All previous recommendations were reviewed, and only those that required updating based on new published studies were revised. Several new recommendations were also added. Recommendations were rated for quality of evidence and were approved by consensus.
There were 15 revised or new recommendations approved by consensus. The revised recommendations included acknowledging that cholinesterase inhibitors (ChEIs) possess a class effect and any of the agents can be used for AD across the spectrum of severity and with co-existing cerebrovascular disease. There was insufficient evidence to recommend for or against the use of ChEIs in combination with memantine for the primary indication of treating neuropsychiatric symptoms, or for the treatment of vascular dementia. Recommendations for the discontinuation of cognitive enhancers were revised and clarified, as well as the risks associated with discontinuing these drugs. ChEIs were recommended as a treatment option for dementia with Parkinson's disease. Risks associated with use of antipsychotics for neuropsychiatric symptoms were strengthened, and guidelines regarding the use of antidepressants for affective disturbances in dementia were weakened, and are now considered an option but not a firm recommendation. Valproate was recommended not to be used, and there was insufficient evidence to recommend for or against the use of selective serotonin reuptake inhibitors or trazodone for the treatment of agitation and aggression.
In spite of the lack of new therapeutic agents for the treatment of dementia, recent studies have helped to clarify and strengthen recommendations to optimize the pharmacological management of these illnesses.
Alzheimer's Research and Therapy 07/2013; 5(Suppl 1):S5. · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zinc is an essential micronutrient with diverse biological roles in cell growth, apoptosis and metabolism, and in the regulation of endocrine, immune, and neuronal functions implicated in the pathophysiology of depression. This study sought to quantitatively summarize the clinical data comparing peripheral blood zinc concentrations between depressed and nondepressed subjects.
PubMed, Cumulated Index to Nursing and Allied Health Literature, and PsycINFO were searched for original peer-reviewed studies (to June 2012) measuring zinc concentrations in serum or plasma from depressed subjects (identified by either screening or clinical criteria) and nondepressed control subjects. Mean (±SD) zinc concentrations were extracted, combined quantitatively in random-effects meta-analysis, and summarized as a weighted mean difference (WMD).
Seventeen studies, measuring peripheral blood zinc concentrations in 1643 depressed and 804 control subjects, were included. Zinc concentrations were approximately -1.85 µmol/L lower in depressed subjects than control subjects (95% confidence interval: [CI]: -2.51 to -1.19 µmol/L, Z17 = 5.45, p < .00001). Heterogeneity was detected (χ(2)17 = 142.81, p < .00001, I(2) = 88%) and explored; in studies that quantified depressive symptoms, greater depression severity was associated with greater relative zinc deficiency (B = -1.503, t9 = -2.82, p = .026). Effect sizes were numerically larger in studies of inpatients (WMD -2.543, 95% CI: -3.522 to -1.564, Z9 = 5.09, p < .0001) versus community samples (WMD -.943, 95% CI: -1.563 to -.323, Z7 = 2.98, p = .003) and in studies of higher methodological quality (WMD -2.354, 95% CI: -2.901 to -1.807, Z7 = 8.43, p < .0001).
Depression is associated with a lower concentration of zinc in peripheral blood. The pathophysiological relationships between zinc status and depression, and the potential benefits of zinc supplementation in depressed patients, warrant further investigation.