Overview
The goal of this clinical trial is to demonstrate potential improvements in clinical trial methods relating to dementia and cognitive decline. The main questions it aims to answer are:
- Can an intervention's outcome be better assessed by a latent variable ("δ") integrating cognitive performance with functional status?
- Can latent biomarkers of δ guide the selection of an intervention that will modulate dementia severity?
- Can a latent variable, derived from information collected remotely from caregivers, preselect subjects most likely to respond to the intervention?
- Is the effect of the intervention in fact medicated by changes in the targeted biomarker?
In this case, the biomarker will be a latent variable derived from several proteins measured in blood (i.e., so-called "adipokines"). The intervention will be donepezil, a medication approved for the treatment of Alzheimer's Disease, but only recently associated with adipokine changes.
Participants with cognitive impairment and their caregivers will be interviewed by telephone and those newly prescribed donepezil by their provider for cognitive impairment will be recruited and enrolled. On the basis of the caregiver's report, the cognitively impaired subjects will be assigned to two groups based on a prediction of their response to donepezil. Researchers will compare those groups to see if dementia severity, as measured by δ, improves in predicted responders, and whether the change in the d-score is mediated by changes in adipokines.
Description
Title: "Novel Methods for Clinical Trials in Dementia and Cognitive Decline"
Study Description: This is a double-blind assignment clinical study to test novel approaches to clinical trial methods. 1) The study team will pre-select cases most likely to benefit from adipokine modulation by a telephone assessment. 2) The study team will pre-select subjects with clinical and preclinical dementia most likely to respond to therapy. 3) The study team will test the drug donepezil's effect on dementia severity, in predicted responders and non-responders, as measured by a latent dementia phenotype "δ' and 4) test a latent Adipokines biomarker construct as a mediator of their association in the predicted responders.
- Objectives
Primary Objective: To assess donepezil's effect on dementia severity as measured by δ in LOI subgroups and across LOI subgroups.
Secondary Objective: To test Adipokines as a mediator of donepezil's effect on dTEL.
Tertiary/Exploratory: To test whether donepezil reverses dementia in cases preselected to by "LOI" analysis.
Eligibility
Inclusion Criteria:
- Ambulatory outpatient volunteers with co-informants.
- Aged 65-100 years
- Clinical diagnosis of AD, or MCI.
- Capacity to give informed consent.
- GDS score (15 item) ≤ 8.
- No significant visual or hearing impairments
- Standardized dECog score between 1.0 and 5.0 relative to ADNI's cohort.
Exclusion Criteria:
- A history of psychosis, including visual hallucinations;
- History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
- History of bradycardia or syncopal events;
- Treatment for cancer in the last 5 years (excluding skin cancers);
- Major surgery in the last year;
- Treatment for a seizure disorder with anticonvulsants;
- Treatment for agitation or psychosis with neuroleptics (treatment of anxiety or insomnia allowed);
- Current treatment with donepezil or any other AChEI or exposure within the last six months
- With a recently started Donepezil Rx (\< 2 weeks), inability to stop Donepezil treatment for 14 days prior to study enrollment.
- AChEI treatment not appropriate due to negative risk/benefit ratio based on medical Hx and symptoms during screening. Evaluated by PI and referring clinician.
- Co-participation in another study that the PI feels would pose a safety risk or adversely affect data integrity of this study.
