Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences.

OBJECTIVE: To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory. METHOD: We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures. RESULTS: Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks. DISCUSSION: Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation.

Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial.

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.

Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial.

BACKGROUND: Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (COX). Although late-life depression in particular has been associated with inflammation, we know of no published studies using COX inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in the treatment of depressive syndromes in this population. OBJECTIVE: To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults. METHODS: The Alzheimer's Disease Anti-inflammatory Prevention Trial was a randomized, placebo-controlled, double-masked clinical trial conducted at six U.S. memory clinics. Cognitively normal volunteers age 70 and older with a family history of Alzheimer-like dementia were randomly assigned to receive celecoxib 200 mg twice daily, naproxen sodium 220 mg twice daily, or placebo. The 30-item version of the Geriatric Depression Scale (GDS) was administered to all participants at enrollment and at yearly follow-up visits. Participants with a GDS score greater than 5 at baseline were classified as depressed. RESULTS: Of 2,528 participants enrolled, 2,312 returned for at least one follow-up visit. Approximately one-fifth had significant depressive symptoms at baseline. Mean GDS score, and the percentage with significant depressive symptoms, remained similar over time across all three treatment groups. Furthermore, there was no treatment effect on GDS scores over time in the subgroup of participants with significant depressive symptoms at baseline. In longitudinal analysis using generalized estimating equations (GEE) regression, higher baseline GDS scores, a prior psychiatric history, older age, time in the study, and lower cognition interacting with time, but not treatment assignment, were associated with significantly higher GDS scores over time. CONCLUSION: Treatment with celecoxib or naproxen did not improve depressive symptoms over time compared with placebo. While inflammation has been implicated in late-life depression, these results do not support the hypothesis that inhibition of the COX pathway with these NSAIDs at these doses alleviates depressive symptoms in older adults.

Sertraline for the treatment of depression in Alzheimer disease: genetic influences.

OBJECTIVE: To assess the potential for genetic influences on sertraline treatment efficacy for depression of Alzheimer disease (dAD). Four functional genetic variants were studied: 2 serotonin receptors (HTR2A-T102C and HTR2C-Cys23Ser), the serotonin transporter (5HTT-LPR), and brain-derived neurotrophic factor (BDNF-Val66Met). Treatment response by genotype was measured by (1) the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, (2) the Cornell scale for Depression in Dementia, and (3) remission of depression. METHODS: We utilized data from the Depression in Alzheimer's Disease Study 2 (DIADS-2), a 24-week, randomized, multicenter trial showing no significant treatment effect of sertraline on dAD. Proportional odds logistic regression and mixed effects models were used to examine the above mentioned outcome measures. RESULTS: No significant interactions were seen between any of the genetic polymorphisms and the selected outcomes above at 12 or 24 weeks. DISCUSSION: Treatment outcomes in the DIADS-2 trial were not significantly influenced by genetic variation at the loci that were assessed. Future studies should continue to examine the interaction of depression-related genetic variants with antidepressant treatment in Alzheimer disease patients with depression.

The synthesis of alternating donor-acceptor polymers based on pyrene-4,5,9,10-tetraone and thiophene derivatives, their composites with carbon, and their lithium storage performances as anode materials.

Two conjugated polymer@activated carbon composites were synthesized by the in situ polymerization of two donor-acceptor type polymers including poly[(thiophene-2,5-yl)-((pyrene-4,5,9,10-tetraone)-2,7-yl)] (PTPT) and poly[((2,3-dihydrothieno[3,4-b][1,4]dioxine)-5,7-yl)-((pyrene-4,5,9,10-tetraone)-2,7-yl)] (POTPT) on activated carbon (AC) by one-step cross-coupling reaction catalyzed by an organometallic catalyst. Cyclic voltammetry showed that both polymers exhibited ambipolar properties, low bandgaps, and low electrode potentials, which could be useful for their application as anodes in lithium-ion battery cells (LIBs). For PTPT@AC and POTPT@AC anodes, they showed a high capacity of 253.9 and 370.5 mA h g-1 at 100 mA g-1. Besides, the capacities of pure polymers were calculated to be 693.5 and 1276.5 mA h g-1 for PTPT and POTPT, respectively, at 100 mA g-1. Compared with PTPT, the introduction of the 3,4-ethylenedioxy unit into the side chain of the thiophene unit leads to substantially improved performance of POTPT due to the lowered LUMO energy levels of POTPT and the electron-rich feature of the EDOT unit. It is suggested that the structure-tuning strategy might be an effective method to prepare the new polymer-based anode for next generation LIBs with high performance and high safety.

Persistence of serum antibodies to Sarcocystis neurona in horses moved from North America to India.

BACKGROUND: The study reported here was undertaken to assess the presence of antibodies to Sarcocystis neurona in the serum of horses of North American origin that had been relocated for 1 year or more to India (ie, outside of the known endemic areas for S. neurona). HYPOTHESIS: The presence or absence of such antibodies should provide information concerning the persistence of such antibodies, or support the presence of chronic infection, or both. ANIMALS: A total of 228 Thoroughbred horses were sampled in India, of which 86 were of North American origin that had been in India between 1 and 13 years, 124 were Indian-born horses that had never been out of India, 8 were of Irish origin, 8 were of English origin, and 2 were originally from France. METHODS: Sera were tested using established western blot analysis. RESULTS: Of the Indian-born horses, 0.8% were test positive, and of the North American horses, 42% were test positive. All of the English and Irish horses were test negative, and the 2 French horses were test positive. CONCLUSIONS AND CLINICAL IMPORTANCE: These data indicate that antibodies against S. neurona can be detected for many years after horses have been removed from an endemic area and that this may be attributable to long half-life of the antibodies or to chronic infection and ongoing antibody production, or both.

The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis.

PURPOSE: To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). METHODS: A case-control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. RESULTS: The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5-17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2-27.9) (P < 0.01). CONCLUSIONS: A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients.

Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

PURPOSE: To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in the era of highly active antiretroviral therapy. DESIGN: Multicenter, prospective, observational study of patients with AIDS. METHODS: Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3 months for outcomes. RESULTS: At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis, 0.014/ 100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates = 21.7 deaths/100 PY [P = .02] and 12.8 deaths/100 PY [P = .04]), respectively, than those for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P = .47). Eyes with newly diagnosed herpetic retinitis appeared to have a poor visual prognosis, with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively). CONCLUSIONS: Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality.