Clinical trial NCT00495820
Conditions: Alzheimer's Disease Apathy Dementia
Keywords: Alzheimer's Disease Apathy Dementia Methylphenidate
Sponsor: VA Office of Research and Development
Start date: 2007-08-01; Completion date: 2010-06-01
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to determine the efficacy of methylphenidate over placebo in treating apathy in patients with Alzheimer's dementia. Apathy is one of the earliest and most profound disturbances that occur in Alzheimer's dementia (AD).

Hypotheses: 1. Methylphenidate (MPH) will improve apathy significantly more than placebo in AD.

2\. Successful treatment of apathy will improve Instrumental Activities of Daily Living (IADLs), and caregiver burden.

Detailed description:
Objective: Apathy is one of the earliest and most profound disturbances that occur in Alzheimer's dementia (AD). Based on promising preliminary data from our open-label pilot study we propose a double blind, placebo-controlled randomized clinical trial of methylphenidate for treatment of apathy in AD.

Research Design: Randomized double blind, placebo-controlled study which will evaluate the effect of methylphenidate on apathy and also the impact of improvement of apathy on caregiver burden and functional status.

Hypotheses: 1. Methylphenidate will improve apathy significantly more than placebo in AD.

2\. Successful treatment of apathy will improve Instrumental Activities of Daily Living (IADLs), and caregiver burden.

Methodology: 60 patients with apathy in the context of AD will be recruited over the next three years. In our proposed study patients will be recruited from relevant clinics at the Omaha Veterans Affairs Medical Center (VAMC) including clinics in Geriatric Psychiatry, Neurology, Primary Care and Geriatric Medicine. 30 patients each with AD and apathy will be randomly assigned to placebo or MPH. All patients in the methylphenidate arm will be started at 5mg twice daily and titrated to 10mg twice daily at two weeks. Patients will be continued in this arm for 12 weeks followed by a 2-week discontinuation phase. Patients will be assessed on regular intervals using the Apathy Evaluation Scale, Instrumental Activities of Daily Living, Zarit Burden Scale and Mini Mental State Examination.

Findings: None, the study is not complete.

Clinical Relationships: While memory is the key cognitive problem in AD, apathy is the key behavioral problem. Apathy is characterized by indifference, disengagement, passivity, and lack of enthusiasm, interest, empathy and interpersonal involvement. Apathy is the most common, one of the earliest and probably the most persistent of behavioral problems in AD. Apathy is the most disturbing behavior to caregivers and has the greatest impact on functional status and caregiver burden.

Despite this, apathy as a behavioral problem has largely been neglected. Most of the research directed towards behavioral problems in dementia is targeted towards more visible behaviors such as agitation, and psychosis. Remarkably, there are no published randomized, double blind, placebo controlled studies in the treatment of apathy associated with AD.

Impact/Significance: Around 1.4 million veterans suffer from apathy in association with AD. Apathy is a strong predictor for functional decline and caregiver burden. Treatment of apathy is remarkably understudied and is absolutely critical to allow veterans to maximize their functional status, social engagement and quality of life, and thus delaying placement in assisted living or nursing home settings.

Arms: arm 1: Methylphenidate arm 2: Placebo
Interventions: intervention 1: Methylphenidate intervention 2: Placebo
Intervention descriptions: intervention 1: Subject will receive 5mg twice a day for two weeks then 10mg twice a day until week 12 of the study. intervention 2: Standard inactive pill.

Protocol documents: