Alzheimer Disease, Dementia
Conditions
Brief summary
The primary goal of this randomized controlled trial (RCT) is to pilot-test a personalized, pragmatic, multi-domain Alzheimer's disease risk reduction intervention in a U.S. integrated healthcare delivery system.
Detailed description
We propose to randomize 200 higher-risk older adults (age 70-89 with low-normal performance on cognitive testing and 2+ modifiable risk factors that will be targeted by our intervention) to a two-year Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT) intervention or a Health Education (HE) control. The SMARRT team will work with participants randomized to the intervention arm to develop a tailored action plan to address risk reduction. Targeted areas will include: increasing physical, mental and social activities; controlling cardiovascular risk factors (diabetes, hypertension); quitting smoking; reducing depressive symptoms; improving sleep; neuroprotective diet; and decreasing use of potentially harmful medications. HE participants will receive periodic handouts on these topics by mail. Changes made to the protocol due to COVID-19, i.e. switching to telephone data collection, will likely limit our ability to examine cognitive change effectively, as several of the most important cognitive tests cannot be administered via telephone.
Interventions
BEHAVIORALSMARRT Intervention
Interventionists will follow a standard protocol for delivering the SMARRT intervention that allows for personalization of the specific risk reduction action plan; these plans will evolve over time according to participant progress, motivation and preferences or newly identified risk factors. Staff will use a tracking database to record information for each participant, including session dates, identified risk factors, motivational barriers and important values, and the outcome of discussions around developing goals. For each participant, the exact number and mode (phone or in-person) of contacts will differ, but we will aim to have at least 1 contact per month with each participant. Best practice will include in-person meetings twice a year during the 2-year intervention period.
BEHAVIORALHealth Education Intervention
Participants randomized to the Health Education (HE) group will receive mailed materials (typically 1-2 pages) every 3 months. This will include general information on Alzheimer's and dementia risk reduction using materials from sources such as the Alzheimer's Association and educational materials commonly provided as part of routine care at Kaiser Permanente Washington (KPWA).
Sponsors
University of California, San Francisco
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants will be randomized after baseline assessments to the SMARRT intervention arm or Health Education (HE) control arm. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white vs. non-white or Hispanic) and age (70-79, 80-89).
Eligibility
Sex/Gender
ALL
Age
70 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* 70-89 Years of Age * Fluent in the English Language * Low-normal performance on a brief telephone cognitive screen, measured using the Cognitive Abilities Screening Instruments (CASI). Low-normal scores are defined as 26-29. * Has at least two additional risk factors that will be targeted by the intervention.
Exclusion criteria
* Residing in a skilled nursing or rehabilitation facility * Receiving palliative care or hospice services * Charlson comorbidity index score of greater than 5 * Bipolar illness or schizophrenia * Current alcohol or drug use disorder * Receiving chronic opioid therapy * Parkinson's disease, amyotrophic lateral sclerosis, or multiple sclerosis * Severe visual or hearing impairment * Requests not to be contacted or not to have their medical record reviewed for research * Prior evidence of dementia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Change | 2 Years | Cognitive function will be measured by the modified Neuropsychological Test Battery (mNTB) global score, which is a composite z-score, an average of z-scores from tests of several cognitive domains. The total score is reported. Higher values signify higher cognitive performance. A z-score of 0 represents the population mean. Treatment effects were estimated using linear mixed models (LMMs) for the changes from baseline to each follow-up assessment (6, 12, 18, and 24 months), with average treatment effects (ATEs) estimated by the average of the four visit-specific between-group differences in adjusted mean change from baseline. Changes made to the protocol due to Covid-19, i.e., switching to telephone data collection, will likely limit our ability to examine cognitive change effectively, as several of the most important cognitive tests cannot be administered via telephone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Targeted Risk Factors | 2 Years | A composite Z-score for risk factors based on the following: the Rapid Assessment of Physical Activity for Older Adult (RAPA), steps per day averaged over 7 days; blood pressure measures averaged for each six-month period for participants with hypertension; the Pittsburgh Sleep Quality Index (PSQI); use of potentially harmful prescription medications; the Center for Epidemiologic Studies - Depression Scale (CES-D); hemoglobin A1c (HbA1c) values averaged over a 12-month time period; the Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction with Social Activities, Short Form; and self-reported smoking. Higher score indicates greater risk factor burden. A z-score of 0 represents the population mean. Treatment effects were estimated using LMMs for the changes from baseline to each follow-up assessment (6, 12, 18, and 24 months), with ATEs estimated by the average of the four visit-specific between-group differences in adjusted mean change from baseline. |
| Quality of Life Measure | 2 Years | Measured with Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health. Higher score indicates better global health and quality of life; range = 0 to 20. |
| Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia | 2 Years | Number of participants at follow up visits with Mild Cognitive Impairment, Alzheimer's Disease, and/or Dementia or with a low score on the Cognitive Abilities Screening Instrument (CASI) (\<27 consistent with cognitive impairment). Lower score indicates poorer cognition; range is 0-33. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SMARRT Intervention The SMARRT intervention team used a standardized procedure to develop an individualized Alzheimer's risk profile for each participant randomized to the SMARRT intervention arm. Participants then met with an interventionist to review their risk profile and develop an initial personalized risk reduction action plan. Targeted areas included: increasing physical, mental and social activities; quitting smoking; healthy diet; controlling cardiovascular risk factors (diabetes, hypertension), including avoiding hypoglycemia in people with diabetes; reducing depressive symptoms; improving sleep; and decreasing use of potentially harmful medications.
SMARRT Intervention: Interventionists will follow a standard protocol for delivering the SMARRT intervention that allows for personalization of the specific risk reduction action plan; these plans will evolve over time according to participant progress, motivation and preferences or newly identified risk factors. Staff will use a tracking database to record information for each participant, including session dates, identified risk factors, motivational barriers and important values, and the outcome of discussions around developing goals. For each participant, the exact number and mode (phone or in-person) of contacts will differ, but we will aim to have at least 1 contact per month with each participant. Best practice will include in-person meetings twice a year during the 2-year intervention period. | 82 |
| Health Education Control Participants in the Health Education arm were mailed general information that addressed factors targeted in the SMARRT intervention, including physical, mental and social engagement; management of cardiovascular risk factors; quitting smoking, healthy diet; depression; sleep; and contraindicated medications. HE participants were not provided with personalized information about their risk of Alzheimer's and dementia.
Health Education Intervention: Participants randomized to the Health Education (HE) group received mailed materials (typically 1-2 pages) every 3 months. This included general information on Alzheimer's and dementia risk reduction using materials from sources such as the Alzheimer's Association and educational materials commonly provided as part of routine care at Kaiser Permanente Washington (KPWA). | 90 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 1 |
| Overall Study | Lost to Follow-up | 7 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 8 |
Baseline characteristics
| Characteristic | SMARRT Intervention | Health Education Control | Total |
|---|---|---|---|
| Age, Continuous | 75.8 Years STANDARD_DEVIATION 4.9 | 75.6 Years STANDARD_DEVIATION 4.6 | 75.7 Years STANDARD_DEVIATION 4.8 |
| Education, years | 16.0 years STANDARD_DEVIATION 2.8 | 16.4 years STANDARD_DEVIATION 2.4 | 16.2 years STANDARD_DEVIATION 2.6 |
| Elixhauser comorbidity score | 2.8 units on a scale STANDARD_DEVIATION 1.9 | 2.3 units on a scale STANDARD_DEVIATION 1.7 | 2.5 units on a scale STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 72 Participants | 134 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 13 Participants | 31 Participants |
| Number of Risk Factors | 2.5 Risk Factors STANDARD_DEVIATION 0.7 | 2.4 Risk Factors STANDARD_DEVIATION 0.6 | 2.5 Risk Factors STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 8 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 64 Participants | 68 Participants | 132 Participants |
| Sex: Female, Male Female | 57 Participants | 51 Participants | 108 Participants |
| Sex: Female, Male Male | 25 Participants | 39 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 82 | 1 / 90 |
| other Total, other adverse events | 14 / 82 | 0 / 90 |
| serious Total, serious adverse events | 24 / 82 | 23 / 90 |
Outcome results
Primary
Cognitive Change
Cognitive function will be measured by the modified Neuropsychological Test Battery (mNTB) global score, which is a composite z-score, an average of z-scores from tests of several cognitive domains. The total score is reported. Higher values signify higher cognitive performance. A z-score of 0 represents the population mean. Treatment effects were estimated using linear mixed models (LMMs) for the changes from baseline to each follow-up assessment (6, 12, 18, and 24 months), with average treatment effects (ATEs) estimated by the average of the four visit-specific between-group differences in adjusted mean change from baseline. Changes made to the protocol due to Covid-19, i.e., switching to telephone data collection, will likely limit our ability to examine cognitive change effectively, as several of the most important cognitive tests cannot be administered via telephone.
Time frame: 2 Years
Population: Participants were all members of Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system in the Seattle area. Eligible participants were KPWA members aged 70-89, who had at least two of the following dementia risk factors targeted by the intervention: physical inactivity, uncontrolled hypertension, poor sleep, taking a prescription medication that may adversely affect cognition, high depressive symptoms, uncontrolled diabetes, social isolation, and current smoking.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SMARRT Intervention | Cognitive Change | 0.34 z-score |
| Health Education Control | Cognitive Change | 0.19 z-score |
p-value: 0.00895% CI: [0.04, 0.26]Mixed Models Analysis
Secondary
Change in Targeted Risk Factors
A composite Z-score for risk factors based on the following: the Rapid Assessment of Physical Activity for Older Adult (RAPA), steps per day averaged over 7 days; blood pressure measures averaged for each six-month period for participants with hypertension; the Pittsburgh Sleep Quality Index (PSQI); use of potentially harmful prescription medications; the Center for Epidemiologic Studies - Depression Scale (CES-D); hemoglobin A1c (HbA1c) values averaged over a 12-month time period; the Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction with Social Activities, Short Form; and self-reported smoking. Higher score indicates greater risk factor burden. A z-score of 0 represents the population mean. Treatment effects were estimated using LMMs for the changes from baseline to each follow-up assessment (6, 12, 18, and 24 months), with ATEs estimated by the average of the four visit-specific between-group differences in adjusted mean change from baseline.
Time frame: 2 Years
Population: Participants were all members of Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system in the Seattle area. Eligible participants were KPWA members aged 70-89, who had at least two of the following dementia risk factors targeted by the intervention: physical inactivity, uncontrolled hypertension, poor sleep, taking a prescription medication that may adversely affect cognition, high depressive symptoms, uncontrolled diabetes, social isolation, and current smoking.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SMARRT Intervention | Change in Targeted Risk Factors | 0.06 z-score |
| Health Education Control | Change in Targeted Risk Factors | -0.05 z-score |
p-value: 0.00295% CI: [0.02, 0.21]Mixed Models Analysis
Secondary
Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia
Number of participants at follow up visits with Mild Cognitive Impairment, Alzheimer's Disease, and/or Dementia or with a low score on the Cognitive Abilities Screening Instrument (CASI) (\<27 consistent with cognitive impairment). Lower score indicates poorer cognition; range is 0-33.
Time frame: 2 Years
Population: Participants were all members of Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system in the Seattle area. Eligible participants were KPWA members aged 70-89, who had at least two of the following dementia risk factors targeted by the intervention: physical inactivity, uncontrolled hypertension, poor sleep, taking a prescription medication that may adversely affect cognition, high depressive symptoms, uncontrolled diabetes, social isolation, and current smoking.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SMARRT Intervention | Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia | 5 Participants |
| Health Education Control | Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia | 8 Participants |
p-value: 0.5295% CI: [0.19, 2.19]Fisher Exact
Secondary
Quality of Life Measure
Measured with Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health. Higher score indicates better global health and quality of life; range = 0 to 20.
Time frame: 2 Years
Population: Participants were all members of Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system in the Seattle area. Eligible participants were KPWA members aged 70-89, who had at least two of the following dementia risk factors targeted by the intervention: physical inactivity, uncontrolled hypertension, poor sleep, taking a prescription medication that may adversely affect cognition, high depressive symptoms, uncontrolled diabetes, social isolation, and current smoking.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SMARRT Intervention | Quality of Life Measure | 12.69 score on a scale |
| Health Education Control | Quality of Life Measure | 11.58 score on a scale |
p-value: 0.0395% CI: [0.08, 2.14]Mixed Models Analysis