STRATEGIES to Improve Memory in Alzheimer's Disease

Improving Memory in Daily Life of Patients With Alzheimer's Disease

Memory mistakes are one of the most detrimental symptoms in Alzheimer's Disease (AD). In this study the investigators will measure the long-term efficacy of memory strategies in patients with AD. First, the efficacy of the strategies will be evaluated in the laboratory by analyzing the behavioral response and the brain activity of the patients. During the first visit, patients will be taught the memory strategies and asked to repeat them at home for 4 weeks. During this period of time, patients will perform several memory tasks while their performance and brain activity will be measured using portable devices. Monitoring brain activity and behavioral responses to memory tasks will provide insightful information on the efficacy of the strategies and allow the investigation of how patients can maintain the strategies over time. The research will examine if improving memory through the use of cognitive strategies, can positively affect other domains of daily life.

Study Overview

• Status: Withdrawn
• Conditions: Alzheimer Disease; Mild Cognitive Impairment; Dementia, Mild
• Intervention / Treatment: Behavioral: Memory strategies in Arm 1; Device: Electroencephalogram (EEG) headset in Arm 1; Other: Tablet in Arm 1; Behavioral: Memory strategies in Arm 2; Device: Electroencephalogram (EEG) headset in Arm 2; Other: Tablet in Arm 2

Detailed Description

A crossover design with two groups will be implemented to test the following objectives:

Primary Objective: To determine the long-term efficacy of memory strategies in AD patients using experimental memory paradigms and standard neuropsychological tests. Over the course of 4 weeks, performance on novel memory tasks and standard neuropsychological tests will evaluate the efficacy of the strategies longitudinally.

Secondary Objectives:

1. To determine the neural mechanism of memory strategies in AD patients through portable electroencephalogram/event-related potential (EEG/ERP) electrophysiology. Portable EEG will allow us to measure the electrophysiological changes associated with the use of memory strategies over time during daily life of patients with AD.
2. To determine how memory strategies, influence the daily life and functioning of the AD patients. Questionnaires on daily life activities will be administered at different timepoints to determine whether patients are able to generalize the strategies to tasks in their daily life.

This research study will investigate whether the use of combined memory strategies (conservative and deep/item-specific encoding) can help improve performance in memory tasks, can be maintained over time, and can be generalized to other tasks in daily life. Depending on the study group, either at week 0 visit or week 2 visit, participants will be trained on the two strategies. A power point presentation will be used to display one example of each of the strategies and how to implement them during the tablet/Ipad tasks. At this time the investigators will answer any other specific questions that might come up about the strategies. Before starting the cognitive tasks at home on the app, the tablet will remind participants about using the strategies, and this will also include an example how the strategies should be implemented.

The two memory strategies will be implemented in the described steps below:

While being presented with a list of items (words or objects), participants will be asked to focus on one unique characteristic of the items (item-specific encoding strategy). Afterwards, another list of items, containing previously studied (old) and unstudied (new) items, will be presented. Participants will be asked to recognize whether the item was presented in the previous list and respond "yes" only if they are absolutely sure of their response (conservative strategy). Participants will then be provided with a number of real-world examples to practice generalizing what they have learned.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For Mild Alzheimer Disease (AD) dementia

• meets probable AD dementia National Institute on Aging and Alzheimer's Association (NIA-AA) criteria
• Mini-Mental State Examination (MMSE) 20-27
• performance on delayed recall and recognition memory worse than 1.5 standard deviation (SD) for age and education
• performance on delayed recall and recognition memory worse than 1.5 SD for age & education in at least one other cognitive domain (e.g., language, executive functioning) based on other tests in our neuropsychological test battery.
• Dr. Turk and Dr. Budson will confirm all mild AD dementia diagnoses

For Mild cognitive impairment (MCI)

• meets MCI due to AD NIA-AA criteria
• MMSE > 23
• performance on delayed recall and recognition memory worse than 1.0 SD for age & education adjusted norms
• Dr. Turk and Dr. Budson will confirm all MCI due to AD diagnoses

Exclusion Criteria:

A clinically significant problem of any of the following conditions:

• depression
• heavy alcohol or drug use
• cerebrovascular disease
• traumatic brain damage
• a different degenerative disease (e.g., fronto-temporal dementia, Parkinson's disease)
• any medical condition whose severity could significantly impair cognition (e.g., organ failure)
• Unable to understand the consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1- 15 Mild AD and 15 MCI due to AD; In Group 1, for the first 2 weeks participants will be taught memory strategies and reminded to use them each day from week 0 to week 2. Weeks 3-4, participants will be advised to keep using the strategies both on the tablet and in their daily life even though they will not be reminded each time they start the task.	Behavioral: Memory strategies in Arm 1; Memory strategies will consist of daily at-home exercises lasting between 20 minutes to 1 hour depending on the memory tasks assigned to each participant. At the start of week 1 participants will be taught the memory strategies to use while completing the daily memory tasks. In week 1 and 2, subjects will be reminded daily to use the memory strategies. At the start of week 3, subjects will be advised to use the memory strategies however they will not be given daily reminders.; Device: Electroencephalogram (EEG) headset in Arm 1; A cap that measures brain activity using a 16-sensor wireless dry (no gel applied) EEG device designed by BrainWaveBank Ltd., that uses Bluetooth technology to securely transmit EEG signals to an Android tablet. The cap will be used during week 1,2,3 and 4.; Other: Tablet in Arm 1; A computer tablet will be provided to each participant that will have daily reminders about the memory strategies during week 1 and 2, while no reminders will be present in week 3 and 4. The tablet software includes a user-friendly interface that provides feedback and instructions that help the participant properly wear the EEG headset. At the end of each session the tablet stores behavioral and EEG data on a secured server accessible by the research staff.
Active Comparator: Group 2- 15 Mild AD and 15 MCI due to AD; In Group 2, for the first 2 weeks participants will be reminded to "try hard" to remember the items although they will not be given any specific strategies. At week 2 the subjects will be taught memory strategies and reminded to use them each day from week 2 to week 4.	Behavioral: Memory strategies in Arm 2; Memory strategies will consist of daily at home exercises lasting between 20 minutes to 1 hour depending on the memory tasks assigned to each participant. During weeks 1 and 2, participants will be completing the memory tasks without being instructed to use any specific strategy. At the end of week 2 subjects will be taught the memory strategies and during week 3 and 4, they will be reminded daily to use the memory strategies while completing the memory tasks.; Device: Electroencephalogram (EEG) headset in Arm 2; A cap that measures brain activity using a 16-sensor wireless dry (no gel applied) EEG device designed by BrainWaveBank Ltd., that uses Bluetooth technology to securely transmit EEG signals to an Android tablet. The cap will be used during week 1,2,3 and 4.; Other: Tablet in Arm 2; A computer tablet will be provided to each participant. During week 3 and 4, the tablet will present daily reminders to use memory strategies while completing the memory tasks. The tablet software includes a user-friendly interface that provides feedback and instructions that help the participant properly wear the EEG headset. At the end of each session the tablet stores behavioral and EEG data on a secured server accessible by the research staff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in performance in memory tasks over time	Change in performance in memory tasks will be measured through daily at home memory exercises that will last from 20 minutes to 1 hour. Higher the scores on the exercise represent better memory performance.	baseline, 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in electroencephalogram (EEG) early negative frontal component (N400)	Change in EEG early negative frontal component (N400) will be assessed by measuring amplitude and latency characteristics of this EEG component. A higher amplitude and shorter latency will show improvement in memory performance.	Baseline, 4 weeks
Change in EEG Late Positive Parietal Component (LPC)	Change in EEG Late Positive Parietal Component (LPC) will be assessed by measuring amplitude and latency characteristics of this EEG component. A higher amplitude and shorter latency will show improvement in memory performance.	Baseline, 4 weeks
Change in EEG Late Positive Frontal Effect (LFE)	Change in EEG Late Positive Frontal Effect (LFE) will be assessed by measuring the amplitude and latency characteristics of this EEG component. A higher amplitude and shorter latency will show improvement in memory performance.	Baseline, 4 weeks
Neuropsychological assessment using the Montreal Cognitive Assessment (MoCA)	Neuropsychological assessment will be completed using the Montreal Cognitive Assessment (MoCA). The MoCA has a total score of 30, and a higher score means improved cognitive performance.	baseline, 4 weeks
Neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).	Neuropsychological assessment will be completed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS has a total index score of 160, and it measures performance in the following domains: immediate memory, visuospatial, language, attention, and delayed memory. A higher score on the RBANS means improved cognitive performance.	Baseline, 4 weeks
Generalization of strategies to daily life functioning	Generalization of strategies will be assessed through the Activities of Daily Living Scale (ADL) which is a 31-item questionnaire assessing the ability to complete activities of daily living. The minimum score is 0 while the maximum score is 279. A lower score on the Activities of Daily life scale means a greater level of independence in completing activities of daily life.	Baseline, 4 weeks
Quality of life with Alzheimer's disease	Quality of life will be assessed with the Quality of Life in Alzheimer's Disease (QoLAD) which is a 13-item questionnaire assessing different aspects of quality of life. The minimum score is 13 and the maximum is 52. A higher score represents better quality of life.	Baseline, 4 weeks
Subjective perception of memory performance	Subjective perception of memory performance will be assessed using the Multifactorial Metamemory Questionnaire (MMQ), which is a 61-item questionnaire divided in three subcategories (Contentment, Ability and Strategy). The minimum score is 0 and the maximum is 244. A higher score means a better subjective memory performance.	Baseline, 4 weeks

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Katherine Turk, MD, BU School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: June 9, 2021
• First Submitted That Met QC Criteria: June 19, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Memory; Memory Strategies; EEG headgear
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement Factor H
• Other Study ID Numbers: H-40597; P30AG013846 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes