2013 AAGP Annual Meeting

Introduction: Evidence suggests an association between serotonin reuptake inhibitors (SRIs) and accelerated bone loss. SRIsand bone metabolism share a common serotonergic mechanism, generating the hypothesis that genetic variation in theserotonin system might modulate bone metabolism changes during SRI treatment. We examined functional genetic poly-morphisms within serotonin receptors involved in bone metabolism, to determine whether they predict changes in bonemetabolism during SRI treatment.Methods: Serum markers of bone formation (P1NP) and resorption (b-CTX) were assayed before and after treatment in 69older adults (age �60) participating in a 12-week, open-label trial of the SRI venlafaxine for major depression. We also gen-otyped participants for putative high- vs low-expressing polymorphisms in the serotonin transporter (5HTT) and serotonin 1Breceptor (5HTR1B) genes.Results: Bone formation was significantly reduced, as measured by decrease in P1NP, with administration of venlafaxine inparticipants with the high-expressing 5HTT genotype and those with the low expressing 5HTR1B genotype. Further analysesrevealed that decrease in P1NP mostly occurred in individuals with the combination of the high-expressing 5HTT genotypeand the low-expressing 5HTR1B genotype.Conclusions: These preliminary findings indicate that genetic variation in serotonin receptors predicts changes in bonemetabolism during SRI use. These results require replication and clinical confirmation; if so, we have identified a geneticsubgroup at high risk for deleterious bone outcomes with the use of serotonergic antidepressants.

Poster Number: NR 41Effects of Methylphenidate on Attention and Association with Apathy in AD patientsKrista Lanctôt, PhD1; Sarah Chau, MSc1; Nathan Herrmann, MD, FRCP(C)1; Lea Drye, PhD2; Paul Rosenberg, MD2;Roberta W. Scherer, PhD2; Vijay Vaidya, MD2; Sandra Black, MA, MD1; Jacobo Mintzer, MD3,4

1Sunnybrook Health Sciences Centre, Toronto, ON, Canada2Johns Hopkins University, Baltimore, MD3Medical University of South Carolina, Charleston, SC4Ralph H. Johnson VA Medical Center, Charleston, SC

Introduction: Apathy, one of the most prevalent neuropsychiatric symptoms in Alzheimer’s Disease (AD), contributessignificantly to further decline in cognition and function. Emerging evidence supports the use of methylphenidate (MPH) forthe treatment of apathy. However, psychostimulants, which increase central dopamine concentrations, are known to play a rolein modulating attention and reward salience. The goal of this study was to investigate the effects of MPH on attention and therelationship between MPH effects on apathy and attention.Methods: Patients were enrolled in the Apathy in Dementia Methylphenidate Trial (ADMET), a randomized, double-blindplacebo-controlled study to examine the safety and efficacy of MPH (10mg PO twice daily) versus placebo for 6 weeks for thetreatment of apathy (Neuropsychiatric Inventory [NPI] Apathy � 4) in AD patients. Apathy was measured with the ApathyEvaluation Scale (AES) and attention with the Wechsler Adult Intelligence Scale - Digit Span (DS) subtest. The DS is comprised ofa forward, backward and total score. Patients were also assessed for overall change (AD Cooperative Study-Global ClinicalImpression of Change, ADCS-CGIC), global cognition (Mini-Mental Status Exam, MMSE) and neuropsychiatric symptoms(NPI). All tests were administered at baseline (prior to randomization) and every 2 weeks over 6 weeks. All analyses were conductedaccording to the intention to treat principle. The treatment effect of MPH on attention measures was assessed by longitudinalanalysis of attention scores using linear mixed effects models with random intercept for each participant. The difference in changein attention measures from baseline to week 6 was compared for MPH and placebo. The effect of baseline attention measure ontreatment response was measured by: i) linear regression models of the change in AES score from baseline to week 6 with baselineattention scores, treatment and their interaction as predictors; ii) logistic regression models of apathy response (defined as decreasein AES scores at week 6 by 3.3 points or more) with and baseline attention scores, treatment group and their interaction aspredictors. Pearson correlation and 95% confidence intervals were calculated for change in attention measures from baseline toweek 6 versus change in apathy measures from baseline to week 6. Improvement in NPI apathy was defined as defined as decreasein NPI apathy score by 1 points or more at week 6. Improvement at CGIC score was defined as any improvement at CGIC scalefrom baseline (minimal, moderate, and marked improvement).Results: Of 60 recruited, 57 patients (34 F, mean�SD age 77�8, MMSE 20�5, NPI Apathy 7�2) completed the study and allavailable data were used in analysis. There were improvements in apathy in MPH group on the CGIC (odds ratio MPH vs. placebo¼3.7 (95% CI: 1.3, 1.08)), NPI apathy (estimated mean score improvement was 1.8 times greater for MPH (95% CIs: 0.3, 3.4)) andAES (estimated difference in change in AES apathy favoring MPH ¼ -2.5 (95% CIs: -6.5, 1.2)). We identified 17 patients withimproved apathy (improvement of at least 3.3 points on the AES) and 40 who did not improve. Estimated difference in change inattention from the baseline to week 6 (d) showed larger improvements (positive d favored MPH) in DS forward score (d ¼ 0.87

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2013 AAGP Annual Meeting

(95% CIs: 0.06-1.08),p¼0.03) and DS total score (d ¼ 1.01 (95% CIs: 0.09-1.93), p¼0.03) in those on MPH. Other attentionmeasures, MMSE and DS backward, also showed larger improvements in the MPH group over placebo; however, theseimprovements were not statistically significant (d for DS backward ¼ 0.17 (95% CIs: -0.66, 1.02) and d for MMSE ¼0.45 (95%CIs: -0.29, 1.21). Further, there was no correlation (Pearson correlation coefficients were not significantly different from zero) forAES versus the attention measures in total and by treatment group. Effect of baseline attention measure on treatment responsemeasured by linear regression model (difference in the slopes) and logistic regression (log odds of improvement in MPH andplacebo group) suggested that that baseline attention scores did not predict apathy response to MPH treatment.Conclusions: These results suggest that while MPH can improve both apathy and attention, the effects are independent in thispatient population. This study provides some insight into the different effects MPH can produce in a heterogeneous diseasesuch as AD.

Poster Number: NR 42

Cognitive Effects of Anticholinergic Medications in Patients with Coronary Artery DiseaseNathan Herrmann, MD; Jordana O’Regan, BSc; Yael B. Schwartz, BSc Candidate; Mahwesh Saleem, MSc;Walter Swardfager, PhD; Krista Lanctôt, PhD

Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Introduction: Coronary artery disease (CAD) is a prominent contributor to medical morbidity in North America and is associatedwith an increased rate of decline in cognitive function as well as representing an independent risk factor for Alzheimer’s disease.Anticholinergic medications are often prescribed in this population to treat a variety of complications and comorbidities. Due to theintrinsic off-target activities and the ability to cross the blood-brain barrier, anticholinergic agents may interfere with cognitiveperformance and lead to central side effects such as cognitive deficits and worsening of symptoms of mild cognitive impairment ordementia.Despite pervasive polypharmacy, the significance of concomitantmedication anticholinergic effects inpredicting objectivecognitive performance has not been quantified in patients with CAD. This cross-sectional observational study of outpatient cardiacrehabilitation patients with CAD aimed to assess the cognitive deficits associated with anticholinergic medication load.Methods: All patients were diagnosed with CAD (defined as participants with: myocardial infarction (MI), angiographicevidence showing � 50% blockage in at least one major coronary artery, percutaneous coronary intervention (PCI), or coronaryartery bypass graft surgery (CABG), and a minimum of 6 weeks post CABG, 6 weeks post MI or 3 weeks post PCI) and enrolledin a 6-month outpatient cardiac rehabilitation program. Demographics, medications and vascular risk factors were assessed foreach patient by interview and chart review. Anticholinergic burden was estimated using the Anticholinergic Cognitive Burden(ACB) scale. A battery of cognitive tests was administered, including the California Verbal Learning test 2nd ed., Revised BriefVisuospatial Memory Test, Stroop, Trail-Making Test Parts A and B, Digit Symbol Coding, FAS test and animal naming.Overall cognition was screened using The Mini-Mental Status Exam.Results: Patients with CAD (n¼131, age 64.2�9.1, 15.3% female) presented with 2.6�1.4 vascular risk factors and were using5.1�1.8 medications. Of those medications, 0.76�0.75 were anticholinergic and patients had an average ACB score of 0.85�0.92.The cognitive tests factored into 3 principle components; verbal memory, visuospatial memory and attention/speed/executivefunction, for which composite Z scores were computed. Controlling for age, gender, years of education, the number of vascularrisk factors and the number of total medications, the ACB was associated with poor attention/speed/executive function (b¼-.227,p¼.010). Anticholinergic burden was not associated with verbal or visuospatial memory scores in adjusted models (p>.05).Conclusions: Anticholinergic exposure was associated with poorer cognitive performance in patients with CAD. Cognitive teststhat depend on attention, psychomotor processing speed and executive function were most sensitive to these effects. Anti-cholinergic beta-blockers frequently prescribed in this population (e.g. metoprolol and atenolol), which are included in theACB, contribute to the utility of this scale in predicting cognitive performance. Avoiding medications with prominentanticholinergic effects in patients with CAD seems feasible and may support cognitive health.

Poster Number: NR 43Assessing Differential diagnosis and symptoms profile of late life psychosis among an elderly populationAli Javadpour, MD

Shiraz university of medical sciences, Shiraz, Islamic Republic of Iran

Introduction: 23% of the older adult experience psychotic symptoms at some time in their aging years. In addition to debateabout the definition of late life psychosis, there are also controversies in regard to conditions causes psychosis in old age

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