Clinical value of Alzheimer's disease biomarker testing.

INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Prevalence of delusions in drug-naïve Alzheimer disease patients: A meta-analysis.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common at all stages of Alzheimer disease (AD). Delusions in AD are associated with negative clinical consequences and may signal rapid disease progression. Hence, we sought to determine the prevalence of delusions in drug-naïve (no cholinesterase inhibitor or neuroleptic medications) AD patients. METHODS: In this meta-analysis, a search of the EMBASE, MEDLINE, and PsycINFO databases was performed. We selected studies reporting delusion prevalence measured by the Neuropsychiatric Inventory (NPI) in drug-naïve AD patients. An aggregate delusion event rate with 95% confidence interval (CI) was calculated. The I2 statistic was used to assess the magnitude of between-study heterogeneity. Single variable meta-regressions allowed examination of the effect of moderating factors and heterogeneity. Quantitative measures were used to appraise for publication bias. RESULTS: We identified 6 studies with 591 participants allowing calculation of the aggregate delusional prevalence rate. Irrespective of dementia severity, the aggregate event rate for delusions was 29.1% (95% CI: 20-41%; I2  = 84.59). No publication bias was observed. CONCLUSION: This meta-analysis calculates a 29.1% prevalence rate of delusions in AD patients. There is a trend towards increasing delusion prevalence in concordance with increasing severity of dementia. Given delusions are associated with poorer outcomes, the obtained prevalence should motivate clinicians to screen carefully for delusions. Current literature limitations warrant future studies, with sub-analyses on dementia severity, and other neurobiological factors known to influence the presence of delusions.

Sex Difference in Aerobic Exercise Efficacy to Improve Cognition in Older Adults with Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial.

Aerobic training (AT) is a promising, non-pharmacological intervention to mitigate the deleterious effects of aging and disease on brain health. However, a large amount of variation exists in its efficacy. This is a secondary analysis of a randomized controlled trial of AT in 71 older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1) whether sex moderates the relationship between AT and executive functions, and 2) the role of brain derived neurotrophic factor (BDNF) and gains in functional fitness capacity. Older adults were randomly assigned to either 6-month, thrice-weekly AT or to usual care plus education (CON). At baseline, trial completion, and 6-month follow-up, executive functions were assessed with the Trail Making Test (A & B), verbal digits forward and backward test, and the Stroop Test. Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared with CON, AT significantly improved Trail Making Test performance in females but not males, an effect that was retained at follow-up. AT significantly increased BDNF levels in females but decreased levels in males. On the other hand, AT led to significant gains in functional fitness capacity in males only. This study provides evidence that sex differences exist in AT efficacy on brain health as well as in the biological mechanisms subserving AT.

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

Aerobic exercise and vascular cognitive impairment: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of a progressive aerobic exercise training program on cognitive and everyday function among adults with mild subcortical ischemic vascular cognitive impairment (SIVCI). METHODS: This was a proof-of-concept single-blind randomized controlled trial comparing a 6-month, thrice-weekly, progressive aerobic exercise training program (AT) with usual care plus education on cognitive and everyday function with a follow-up assessment 6 months after the formal cessation of aerobic exercise training. Primary outcomes assessed were general cognitive function (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog]), executive functions (Executive Interview [EXIT-25]), and activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]). RESULTS: Seventy adults randomized to aerobic exercise training or usual care were included in intention-to-treat analyses (mean age 74 years, 51% female, n = 35 per group). At the end of the intervention, the aerobic exercise training group had significantly improved ADAS-Cog performance compared with the usual care plus education group (-1.71 point difference, 95% confidence interval [CI] -3.15 to -0.26, p = 0.02); however, this difference was not significant at the 6-month follow-up (-0.63 point difference, 95% CI -2.34 to 1.07, p = 0.46). There were no significant between-group differences at intervention completion and at the 6-month follow-up in EXIT-25 or ADCS-ADL performance. Examination of secondary measures showed between-group differences at intervention completion favoring the AT group in 6-minute walk distance (30.35 meter difference, 95% CI 5.82 to 54.86, p = 0.02) and in diastolic blood pressure (-6.89 mm Hg difference, 95% CI -12.52 to -1.26, p = 0.02). CONCLUSIONS: This study provides preliminary evidence for the efficacy of 6 months of thrice-weekly progressive aerobic training in community-dwelling adults with mild SIVCI, relative to usual care plus education. CLINICALTRIALSGOV IDENTIFIER: NCT01027858. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults with mild SIVCI, an aerobic exercise program for 6 months results in a small, significant improvement in ADAS-Cog performance.

Endocrine treatment-associated cognitive impairment in breast cancer survivors: evidence from published studies.

Endocrine-based treatments are the mainstay of therapy for postmenopausal women with breast cancer; yet concern has been raised about potential adverse cognitive effects. We performed a systematic review of the published literature to evaluate whether endocrine-based treatments for breast cancer are associated with changes in cognitive domains and whether these effects are more pronounced with advanced age. An electronic database search was performed. Original investigations that examined the effects of endocrine treatment on cognitive function were identified. Data were abstracted and studies were assessed for risk of bias. A total of 21 unique studies (n = 2398) were identified. Ten were short-term (duration ≤ 2 years) and 11 were long-term (duration > 2 years). Nine (43 %) studies had a sample size ≤100 subjects; 9 (43 %) were longitudinal, with baseline measurement before treatment initiation. No studies were primary randomized clinical trials. While there was heterogeneity in the neuropsychological measures used, tests could be grouped into the cognitive domains that they assessed. Compared to breast cancer or healthy controls, endocrine therapy was associated with impaired performance on neuropsychological testing. No study explored the association between age and changes in cognitive performance. Overall, endocrine therapies were associated with greater cognitive deficits compared to surgical and healthy controls; yet, lack of randomized trial data and heterogeneity in design of many studies limited any definitive conclusions. Despite older women being at highest risk for the development of cognitive impairment, advanced age has not been adequately explored.

Effect of selective serotonin reuptake inhibitors in Alzheimer's disease with comorbid depression: a meta-analysis of depression and cognitive outcomes.

BACKGROUND: Comorbid depression is a leading neuropsychiatric complication in the Alzheimer's disease (AD) syndrome. In 2011, diagnostic criteria for AD were revised to include neuropsychiatric symptoms. It has been proposed that adding an antidepressant to existing treatment for AD could provide relief for not only depressive but also cognitive symptoms. OBJECTIVE: The aim was to quantitatively review published studies to examine the efficacy of selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) therapy for alleviation of comorbid, diagnosed depression as well as cognitive decline in AD. METHODS: A search of electronic databases was performed. Studies were retained for analysis if SSRI/SNRI antidepressant therapy was compared with placebo among AD patients with comorbid depression. Effect-size (ES) estimates (Hedges' g) were calculated using Comprehensive Meta-Analysis software. RESULTS: From 598 examined studies, 12 SSRI studies met the inclusion criteria, and from these, only six met all criteria, among which five reported sufficient and consistent data to be included in the meta-analysis. Within a random effect model, ES estimates of the first and second nested global analyses were non-significant, non-heterogeneous and small to null at the endpoint for depression, favouring SSRIs, -0.06 and -0.10, respectively (p > 0.05). The ES for global cognition as measured by the Mini-Mental State Examination was negligible (ES = 0.001). CONCLUSIONS: Current evidence does not support the efficacy of SSRI treatment for symptoms of comorbid depression in AD. However, studies differed in terms of criteria for diagnosis of depression, the compound tested and outcome measures for depression. These factors could account for the lack of a clear benefit for depression.

Cost-effectiveness: cholinesterase inhibitors and memantine in vascular dementia.

BACKGROUND: Several randomized controlled trials of cholinesterase inhibitors and memantine in mild to moderate vascular dementia have demonstrated the efficacy of these treatments. However, given these drugs incur considerable cost, the economic argument for their use is less clear. OBJECTIVE: To determine the incremental cost-effectiveness of cholinesterase inhibitors and memantine for mild to moderate vascular dementia. DESIGN: A decision analysis model using a 24-28 week time horizon was developed. Outcomes of cholinesterase inhibitors and memantine and probabilities of adverse events were extracted from a systematic review. Costs of adverse events, medications, and physician visits were obtained from local estimates. Robustness was tested with probabilistic sensitivity analysis using a Monte Carlo simulation. INTERVENTIONS: Donepezil 5 mg daily, donepezil 10 mg daily, galantamine 16-24 mg daily, rivastigmine flexible dosing up to 6 mg twice daily, or memantine 10 mg twice daily versus standard care. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) expressed as cost per unit decrease in the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale. RESULTS: Donepezil 10 mg daily was found to be the most cost-effective treatment with an ICER of $400.64 (95%CI, $281.10-$596.35) per unit decline in the ADAS-cog subscale. All other treatments were dominated by donepezil 10 mg, that is, more costly and less effective. CONCLUSION: From a societal perspective, treatment with cholinesterase inhibitors or memantine was more effective but also more costly than standard care for mild to moderate vascular dementia. The donepezil 10 mg strategy was the most cost-effective and also dominated the other alternatives.

Antipsychotic drug use and mortality in older adults with dementia.

BACKGROUND: Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety. OBJECTIVE: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality. DESIGN: Population-based, retrospective cohort study. SETTING: Ontario, Canada. PATIENTS: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003. MEASUREMENTS: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status. RESULTS: A total of 27,259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations. LIMITATIONS: Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations. CONCLUSIONS: Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia.

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.

Atypical antipsychotics and parkinsonism.

BACKGROUND: Atypical antipsychotic agents are thought to be less likely than older typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed atypical relative to typical antipsychotics. METHODS: Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. RESULTS: All 25,769 older adults prescribed antipsychotics were observed for 11,573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an atypical antipsychotic, those dispensed a typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency typical antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to atypical antipsychotics. Relative to those dispensed a high-dose atypical antipsychotic, those dispensed a typical antipsychotic were at similar risk for parkinsonism (Wald chi(2) = 0.14, P = .7). CONCLUSIONS: The risk of development of parkinsonism associated with the use of high-dose atypical antipsychotics was similar to that associated with the use of typical antipsychotics. Caution should be used when prescribing atypical antipsychotic therapy at high doses.

Antipsychotic medications and drug-induced movement disorders other than parkinsonism: a population-based cohort study in older adults.

OBJECTIVES: To study the relationship between initiating therapy with an antipsychotic medication and a subsequent new diagnosis of a drug-induced movement disorder other than parkinsonism in older adults with dementia. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Ontario residents aged 66 and older with a diagnosis of dementia newly started on treatment with typical or atypical antipsychotic therapy. MEASUREMENT: Estimated relative risk of developing a drug-induced movement other than parkinsonism in the 1-year follow-up period after starting therapy with an antipsychotic medication. RESULTS: From April 1, 1997, to March 31, 2001, 21, 835 older adults with dementia who were newly started on antipsychotic medications were identified. Nine thousand seven hundred ninety subjects were started on atypical antipsychotics and 12,045 subjects started on typical antipsychotics. Demographic characteristics were similar between the groups. There were 5.24 cases of tardive dyskinesia (TD) or other drug-induced movement disorder per 100 person-years on therapy with a typical antipsychotic and 5.19 cases per 100 person-years on therapy with an atypical antipsychotic. The risk of developing drug-induced movement disorder while being treated with an atypical agent was not statistically different from that with a typical antipsychotic (relative risk=0.99, 95% confidence interval=0.86-1.15; P<.93). CONCLUSION: Older adults with dementia who are treated with typical or atypical antipsychotic therapy are at risk for developing TD and other drug-induced movement disorders.

A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs.

BACKGROUND: The prescribing cascade model involves the misinterpretation of an adverse reaction to 1 drug and the subsequent, potentially inappropriate prescription of a second drug. We present a new example of the prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs used to manage urinary incontinence. METHODS: A population-based retrospective cohort study was carried out in Ontario, Canada. Participants included 44,884 older adults with dementia (20,491 were dispensed a cholinesterase inhibitor and 24,393 were not), enrolled between June 1, 1999, and March 31, 2002. Subjects were observed until they received an anticholinergic drug, stopped the cholinesterase inhibitor treatment, died, or the study period ended (March 31, 2003). The main outcome measure was receipt of an anticholinergic drug to manage urinary incontinence. RESULTS: After adjusting for potential confounding factors, we observed that older adults with dementia who were dispensed cholinesterase inhibitors had an increased risk of subsequently receiving an anticholinergic drug (4.5% vs 3.1%; P<.001; adjusted hazard ratio, 1.55; 95% confidence interval, 1.39-1.72), relative to those not receiving cholinesterase inhibitors. This finding was consistent in a series of subgroup analyses. CONCLUSIONS: Use of cholinesterase inhibitors is associated with an increased risk of receiving an anticholinergic drug to manage urinary incontinence. The use of an anticholinergic drug in this setting may represent a clinically important prescribing cascade. Clinicians should consider the possible contributing role of cholinesterase inhibitors in new-onset or worsening urinary incontinence and the potential risk of coprescribing cholinesterase inhibitors and anticholinergic drugs to patients with dementia.

New thyroxine treatment in older adults beginning lithium therapy: implications for clinical practice.

OBJECTIVE: The authors sought to determine the incidence of lithium-induced hypothyroidism in a population-based cohort of older adults beginning lithium therapy and thereby to inform clinical guidelines on the frequency of monitoring necessary in this group. METHODS: The authors conducted a population-based observational cohort study using four administrative databases that contained information on over 1.3 million older adults in Ontario who receive universal healthcare coverage in terms of physician services, drugs, and hospitalizations. Over an 18-month period, they studied adults age>or=65 who were newly prescribed lithium or valproate, monitoring subjects for initiation of T4 therapy (as a proxy for hypothyroidism) while they continued their lithium use. RESULTS: The authors identified 1,705 new users of lithium and 2,406 new users of valproate with similar baseline characteristics. Lithium users were significantly more likely to be treated with T4 than were valproate users. The rate of T4 treatment per 100 person-years was 5.65 in the lithium group and 2.70 in the valproate group. CONCLUSION: T4 treatment was initiated in almost 6% of lithium-treated patients, suggesting the possibility that hypothyroidism developed twice as frequently among these patients as would be expected among a mixed-age population. Increased vigilance and continued monitoring of thyroid functioning for at least 2 years is necessary in older adults beginning lithium therapy.

Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study.

OBJECTIVE: To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada. Patients 32,710 older adults (< or = 65 years) with dementia (17,845 dispensed an atypical antipsychotic and 14,865 dispensed a typical antipsychotic). MAIN OUTCOME MEASURES: Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. RESULTS: After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. CONCLUSION: Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.

Teaching physicians geriatric principles: a randomized control trial on academic detailing plus printed materials versus printed materials only.

BACKGROUND: We compared the effectiveness of academic detailing with printed materials, versus printed materials only, on promoting geriatric knowledge among physicians. METHODS: 31 physicians were randomly assigned to receive academic detailing plus printed materials (group 1 intervention, n = 16), or printed materials alone (group 2 control, n = 15), on 5 geriatric topics identified from a needs assessment survey. Two participants withdrew from group 2, leaving 13 in the control group. Both groups received printed educational materials between baseline and time 1, and at time 2. Only group 1 received an additional 15-minute, one-on-one education session with a geriatrician at time 2. The primary endpoint was knowledge retention, measured by the numeric score of a 5-item questionnaire (range 0 to 5), comprised of items from the Geriatrics Knowledge Test. Knowledge retention was measured at baseline, 1 week (time 1), and on average 29 weeks later (time 2). RESULTS: Most participants were postgraduate trainees. The mean knowledge score in all participants decreased from 3.6 +/- 1.2 at baseline to 3.1 +/- 1.2 at time 1 (p =.006). 19 participants (9 in group 1 and 10 in group 2) completed the knowledge questionnaire at time 2. At baseline, group 1 scored lower than group 2 (3.4 +/- 1.3 versus 3.8 +/- 1.1, p =.39); whereas at time 2, group 1 scored significantly higher than group 2 (4.7 +/- 0.7 versus 3.9 +/- 0.7, p =.034). Academic detailing plus printed materials produced higher mean score change from baseline (1.1 +/- 1.3) than printed materials alone (0.0 +/- 1.1, p =.053). CONCLUSIONS: Academic detailing plus printed materials improved knowledge retention among physicians, whereas printed materials only did not.

Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review.

OBJECTIVE: To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD). DATA SOURCES: Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials. STUDY SELECTION: Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD. REVIEW METHODS: Two reviewers assessed trial validity independently. DATA EXTRACTION: Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events. RESULTS: 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution (> 96%), elderly (weighted mean 82.3 years), and had Alzheimer's disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait. CONCLUSIONS: Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.