Apathy is defined as a loss of will and initiative, lack of interest in activities, lack of productivity, as well as limited affective response to positive r negative elements . Apathy is one of the most common neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD), affecting approximately 70% of AD patients and resulting in serious adverse consequences for patients and caregivers. Apathetic patients are also more likely to require institutionalization, the largest single driver of direct costs in AD. Despite the high prevalence of apathy in AD and its serious consequences, there are no proven treatments for this condition. Nonpharmacologic strategies appear to have limited effects on apathy in AD, as do current FDA-approved medications for AD such as cholinesterase inhibitors. Recently, new research has suggested the involvement of dopamine pathways in the biology of apathy in AD and the potential value of dopamine enhancers, such as methylphenidate, for the treatment of this condition. Moreover, we have recently reported the results of two six- week randomized controlled trials showing a clear benefit of methylphenidate over placebo in treating apathy in AD, as well as potential cognitive benefits of methylphenidate and a favorable safety/tolerability profile. [However, a number of key questions relevant for clinical practice were not answered by these studies. For example, is the treatment effective and safe beyond six weeks in a larger sample? Can the potential cognitive benefit of methylphenidate be reproduced and remain clinically significant in this population? Can the combination of a decrease in apathy and an improvement in cognition be translated to clinically significant functional change? Does the treatment of apathy in AD have an impact on subject quality of life and pharmacoeconomics? We propose to address these questions by conducting a multi-site, parallel, randomized, double-blind, placebo-controlled study evaluating methylphenidate for the treatment of apathy in AD patients (Apathy in Dementia Methylphenidate Trial-II (ADMET II)) in a larger sample, over a more extensive period of time and employing a concise battery of neuropsychological tests optimized for apathetic AD patients. The ultimate goal is to collect evidence strong enough to support a change in clinical practice. This trial will bring together a team of investigators who have collaborated successfully in the execution of the first ADMET study as well as other clinical trials exploring treatments for neuropsychiatric symptoms of dementia.]

Public Health Relevance

Apathy affects over 70% of patients suffering from Alzheimer's disease (AD) resulting in excess disability for the patient, caregiver burden, and high emotional and economic costs to society. Today, there is no current approved treatment for apathy in AD. This application aims to provide information that will allow methylphenidate, a widely available generic drug, to become the first treatment for apathy in AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG046543-04
Application #
9293951
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Ryan, Laurie M
Project Start
2014-09-15
Project End
2019-05-31
Budget Start
2017-07-01
Budget End
2018-05-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Other Health Professions
Type
Sch Allied Health Professions
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
Desmarais, Philippe; Miville, Catherine; Milán-Tomás, Ángela et al. (2018) Age representation in antiepileptic drug trials: A systematic review and meta-analysis. Epilepsy Res 142:9-15
Scherer, Roberta W; Drye, Lea; Mintzer, Jacobo et al. (2018) The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial. Trials 19:46
Babulal, Ganesh M; Quiroz, Yakeel T; Albensi, Benedict C et al. (2018) Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement :
Desmarais, Philippe; Lanctôt, Krista L; Masellis, Mario et al. (2018) Social inappropriateness in neurodegenerative disorders. Int Psychogeriatr 30:197-207
Sherman, Chelsea; Liu, Celina S; Herrmann, Nathan et al. (2018) Prevalence, neurobiology, and treatments for apathy in prodromal dementia. Int Psychogeriatr 30:177-184
Lanctôt, Krista L; Agüera-Ortiz, Luis; Brodaty, Henry et al. (2017) Apathy associated with neurocognitive disorders: Recent progress and future directions. Alzheimers Dement 13:84-100
Liu, Celina S; Ruthirakuhan, Myuri; Chau, Sarah A et al. (2016) Pharmacological Management of Agitation and Aggression in Alzheimer's Disease: A Review of Current and Novel Treatments. Curr Alzheimer Res 13:1134-44
Rej, Soham; Saleem, Mahwesh; Herrmann, Nathan et al. (2016) Serum low-density lipoprotein levels, statin use, and cognition in patients with coronary artery disease. Neuropsychiatr Dis Treat 12:2913-2920