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Dive into the research topics where Laura Jakimovich is active.

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Featured researches published by Laura Jakimovich.


American Journal of Geriatric Psychiatry | 2001

Placebo-Controlled Study of Divalproex Sodium for Agitation in Dementia

Anton P. Porsteinsson; Pierre N. Tariot; Rosemary Erb; Christopher Cox; Elizabeth Smith; Laura Jakimovich; John Noviasky; Nancy Kowalski; Connie Holt; Carrie Irvine

The authors assessed the efficacy, tolerability, and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week, randomized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium. Participants were blinded to treatment except for a physician-monitor and a pharmacist. When several covariates were taken into account, the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant (P=0.05). Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale, vs. 52% on placebo (P=0.06 in the adjusted analysis). Side effects occurred in 68% of the divalproex group vs. 33% of the placebo group (P=0.03) and were generally rated as mild. This placebo-controlled study, despite some limitations, suggests possible short-term efficacy, tolerability, and safety of divalproex for agitation in dementia and supports further placebo-controlled studies.


Lancet Neurology | 2012

Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study.

Adam S. Fleisher; Kewei Chen; Yakeel T. Quiroz; Laura Jakimovich; Madelyn Gutierrez Gomez; Carolyn M. Langois; Jessica B. Langbaum; Napatkamon Ayutyanont; Auttawut Roontiva; Pradeep Thiyyagura; Wendy Lee; Hua Mo; Liliana Lopez; Sonia Moreno; Natalia Acosta-Baena; Margarita Giraldo; Gloria María Gallego García; Rebecca Reiman; Matthew J. Huentelman; Kenneth S. Kosik; Pierre N. Tariot; Francisco Lopera; Eric M. Reiman

BACKGROUND Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimers disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimers disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease. METHODS Between Aug 1 and Dec 6, 2011, members of the familial Alzheimers disease Colombian kindred aged 18-60 years were recruited from the Alzheimers Prevention Initiatives registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimers Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition. FINDINGS We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3-33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. (18)F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3-40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions. INTERPRETATION These findings contribute to the understanding of preclinical familial Alzheimers disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimers disease. FUNDING Avid Radiopharmaceuticals, Banner Alzheimers Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.


Archives of General Psychiatry | 2011

Chronic Divalproex Sodium to Attenuate Agitation and Clinical Progression of Alzheimer Disease

Pierre N. Tariot; Lon S. Schneider; Jeffrey L. Cummings; Ronald G. Thomas; Rema Raman; Laura Jakimovich; Rebekah Loy; Barbara Bartocci; Adam S. Fleisher; M. Saleem Ismail; Anton P. Porsteinsson; Michael W. Weiner; Clifford R. Jack; Leon J. Thal; Paul S. Aisen

CONTEXT Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate). OBJECTIVE To determine whether treatment with valproate could delay or prevent emergence of agitation or psychosis. DESIGN, SETTING, AND PATIENTS A multicenter, randomized, double-blind, placebo-controlled trial of flexible-dose valproate in 313 (of 513 screened) individuals with moderate Alzheimer disease who had not yet experienced agitation or psychosis. The study was conducted from November 1, 2005, through March 31, 2009, at 46 sites in the United States. INTERVENTION Participants were randomly assigned to valproate treatment at a target dose of 10 to 12 mg per kilogram of body weight per day or identical-appearing placebo for 24 months followed by a 2-month period of single-blind placebo treatment. MAIN OUTCOME MEASURE Time to emergence of clinically significant agitation or psychosis. RESULTS A total of 122 participants (59 receiving valproate and 63 receiving placebo) completed 24 months of treatment while taking study medication; 42 (27 receiving valproate and 15 receiving placebo) reached 24 months having discontinued study medication; 150 reached month 26. There was no difference between groups in time to emergence of agitation or psychosis (Cox proportional hazard ratio, 0.96; P = .88). There was no difference between groups in change on any secondary outcome. The valproate group had higher rates of somnolence, gait disturbance, tremor, diarrhea, and weakness. Eighty-eight participants underwent magnetic resonance imaging scans at baseline and 12 months; the valproate group showed greater loss in hippocampal and whole-brain volume, accompanied by greater ventricular expansion (P < .001). CONCLUSION Valproate treatment did not delay emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer disease and was associated with significant toxic effects.


American Journal of Geriatric Psychiatry | 2005

Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation A Randomized, Controlled Trial

Pierre N. Tariot; Rema Raman; Laura Jakimovich; Lon S. Schneider; Anton P. Porsteinsson; Ronald G. Thomas; Jacobo Mintzer; Ronald Brenner; Kim Schafer; Leon J. Thal

OBJECTIVE Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimers Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia. METHODS This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability. RESULTS Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences. CONCLUSIONS This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.


JAMA Neurology | 2015

Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study

Adam S. Fleisher; Kewei Chen; Yakeel T. Quiroz; Laura Jakimovich; Madelyn Gutierrez Gomez; Carolyn M. Langois; Jessica B. Langbaum; Auttawut Roontiva; Pradeep Thiyyagura; Wendy Lee; Napatkamon Ayutyanont; Liliana Lopez; Sonia Moreno; Claudia Muñoz; Victoria Tirado; Natalia Acosta-Baena; Anne M. Fagan; Margarita Giraldo; Gloria María Gallego García; Matthew J. Huentelman; Pierre N. Tariot; Francisco Lopera; Eric M. Reiman

IMPORTANCE Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and noncarriers from the worlds largest known autosomal dominant Alzheimer disease (AD) kindred. OBJECTIVE To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). MAIN OUTCOMES AND MEASURES We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. RESULTS Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindreds estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma Aβ1-42 or Aβ1-40. CONCLUSIONS AND RELEVANCE This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD.


American Journal of Geriatric Psychiatry | 2003

Valproate therapy for Agitation in dementia: Open-label extension of a double-blind trial

Anton P. Porsteinsson; Pierre N. Tariot; Laura Jakimovich; Nancy Kowalski; Connie Holt; Rosemary Erb; Christopher Cox

OBJECTIVE The authors describe an open-label extension of a double-blind, randomized, placebo-controlled study of divalproex sodium in 56 nursing home patients with agitation and dementia. METHODS Participants (N=46) were treated for 6 weeks in an open fashion with clinically optimal doses of divalproex sodium (range: 250 mg/day-1,500 mg/day; mean: 851 mg/day). Behavior was assessed with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Change (CGI) by new raters. Safety, tolerability, and laboratory data were obtained regularly. RESULTS The mean BPRS Agitation Factor decreased by 3.1 points from baseline; 86% of those completing the open phase were rated as improved on the CGI. These changes were mirrored by changes in other behavior rating scales. Sixty percent of subjects had no side effects; 33% had side effects that were rated as mild. There were no clinically significant changes in laboratory values. CONCLUSION Ongoing open-label treatment with divalproex was associated with improvement in measures of agitation. Doses, levels, and tolerability were similar to those in the blinded phase of the study. These findings help confirm and extend the results from the placebo-controlled phase of the trial and suggest that divalproex may be beneficial for some patients with this clinical problem.


Current Alzheimer Research | 2005

A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Safety and Tolerability of Two Doses of Divalproex Sodium in Outpatients with Probable Alzheimers Disease

Louis A. Profenno; Laura Jakimovich; Connie Holt; Anton P. Porsteinsson; Pierre N. Tariot

OBJECTIVE: The Alzheimers Disease Cooperative Study (ADCS) is conducting a clinical trial to address whether chronic valproate treatment can delay emergence of behavioral symptoms in outpatients with AD. Since there were no data on the safety and tolerability of divalproex sodium in outpatients with dementia, we undertook a pilot study to inform the design of the ADCS study. METHODS: We recruited 20 outpatients with probable AD, MMSE 10-20, without history of agitation or psychosis. This was a 10-week randomized, double-blind, placebo-controlled study assessing the safety and tolerability of 1,000 mg/day and 1,500 mg/day of divalproex sodium delayed-release for 8 weeks followed by extended-release for 2 weeks. Other outcome measures addressed cognition, function, global status, side effects, and laboratory data. RESULTS: Participants assigned to active treatment ingested approximately 30% less of their prescribed study medication compared to those receiving placebo (p < .05 Wilcoxon Rank Sum test). The average tolerated dose for all participants at week 8 was 810 mg/day or 11.5 mg/kg/day, similar to the dose tolerated by nursing home patients. The most common side effects were sleepiness and tiredness, with worse cognitive performance in those assigned to 1500 mg/day. CONCLUSIONS: These results were used to design the multi-center ADCS trial. Doses of less than 1000 mg/day of divalproex sodium were the maximum tolerated by these outpatients with AD. A larger study of divalproex sodium dose tolerability is needed to define treatment in outpatients with Alzheimers disease.


Journal of the American Medical Directors Association | 2003

Donepezil Use for Advanced Alzheimer's Disease—A Case Study from a Long-term Care Facility

Pierre N. Tariot; Laura Jakimovich

The following case describes a severely demented, elderly male patient who was placed in a nursing home when he became unmanageable in an assisted-living facility. Upon admission to the nursing facility, the patient was diagnosed with relatively severe Alzheimers disease (AD)treated with the cholinesterase inhibitor donepezil in the context of a clinical study. This report illustrates that donepezil, and perhaps by analogy other cholinesterase inhibitors as well, can be efficacious in treating the cognitive, functional, and behavioral impairment associated with advanced AD.


Alzheimers & Dementia | 2012

THE ALZHEIMER'S PREVENTION INITIATIVE

Pierre N. Tariot; Carole Ho; Carolyn Langlois; Eric M. Reiman; Francisco Lopera; Jessica B. Langbaum; Laura Jakimovich; Napatkamon Ayutyanont; Nellie High; Robert Paul; Shehnaaz Suliman; Silvia Rios Romenets; William Cho

genic animal experiments suggest that we may be testing anti-Ab therapies much too late in the pathophysiological process of Alzheimer’s disease (AD). Converging data from PETamyloid imaging, cerebrospinal fluid studies, and large autopsy series suggest that approximately one-third of clinically normal older individuals harbor a substantial burden of cerebral amyloid-b. These amyloid-positive “normals” demonstrate evidence of functional and structural imaging abnormalities, elevation of CSF tau, and subtle cognitive deficits, consistent with the preclinical stages of AD, and represent an ideal population for a large secondary prevention effort to slow cognitive decline. Methods: The Alzheimer’s Disease Cooperative Study (ADCS) is proposing a placebo-controlled, 3-year trial in clinically normal older individuals with biomarker evidence of AD pathology. The primary outcome will be slowing the rate of decline on a cognitive composite, with multiple biomarkers as secondary outcomes. Eligible subjects will be clinically normal (CDR 0, MMSE 27-30), over age 70, and will have evidence of amyloid-positivity on PET amyloid imaging. The choice of treatment has not yet been finalized, but will be a monoclonal antibody with clear evidence of target engagement and adequate safety data to support a 3-year trial.Results:Analyses using available data from the Alzheimer’s Disease Neuroimaging Initiative and Australian Imaging Biomarkers Lifestyle study consistently demonstrate evidence of an increased rate of cognitive decline in amyloid-positive normals, and that approximately n1⁄4500 subjects per arm will yield adequate power to detect a 25-35% treatment-related decrease in the rate of cognitive decline. We will also include a natural history arm of 500 amyloid-negative individuals to investigate the specific pattern of “amyloid-related” decline and to develop more sensitive outcome measures to improve the efficiency of future secondary prevention trials in preclinical AD.Conclusions:TheA4 trial will provide complementary information to the prevention initiatives being planned in genetic-risk cohorts. Although amyloid-b may be only one of several pathogenic factors in the elderly population, we now have the biomarker tools and biologically active compounds to test the hypothesis that altering “upstream” amyloid burden will impact “downstream” neurodegeneration and delay or prevent cognitive decline.


Alzheimer's & Dementia: Translational Research & Clinical Interventions | 2018

Adherence/Retention Alzheimer's Prevention Initiative Colombia Plan

Silvia Rios-Romenets; Natalia Acosta-Baena; Liliana Lopez; Lucia Madrigal-Zapata; Helen Street; Laura Jakimovich; Jessica B. Langbaum; William Cho; Eric M. Reiman; Pierre N. Tariot; Francisco Lopera

The Alzheimers Prevention Initiative Colombia Trial is a collaborative project involving the Neurosciences Group of Antioquia, Genentech/Roche, and the Banner Alzheimers Institute, studying whether crenezumab can delay or prevent the clinical onset of Alzheimers disease in cognitively unimpaired individuals who carry the PSEN1 E280A mutation. In an effort to optimize participant compliance and adherence and maintain interest in the trial for its duration, the Neurosciences Group of Antioquia developed an “Adherence/Retention Plan.” This plan identifies potential barriers to trial adherence related to characteristics of the participants and study partners, protocol design, sponsors, investigators, environmental factors, and characteristics of this population in general and identifies potential solutions to these barriers.

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Pradeep Thiyyagura

Good Samaritan Medical Center

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Kewei Chen

Beijing Normal University

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