Trial Outcomes & Findings for Systematic Multi-domain Alzheimer's Risk Reduction Trial (NCT NCT03683394)

Last Updated: 2023-09-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

172 participants

Primary outcome timeframe

2 Years

Results posted on

2023-09-21

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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).
Overall Study STARTED	82	90
Overall Study COMPLETED	68	81
Overall Study NOT COMPLETED	14	9

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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).
Overall Study Withdrawal by Subject	4	8
Overall Study Lost to Follow-up	7	0
Overall Study Death	3	1

Baseline Characteristics

Systematic Multi-domain Alzheimer's Risk Reduction Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SMARRT Intervention n=82 Participants 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.	Health Education Control n=90 Participants 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).	Total n=172 Participants Total of all reporting groups
Age, Continuous	75.8 Years STANDARD_DEVIATION 4.9 • n=93 Participants	75.6 Years STANDARD_DEVIATION 4.6 • n=4 Participants	75.7 Years STANDARD_DEVIATION 4.8 • n=27 Participants
Sex: Female, Male Female	57 Participants n=93 Participants	51 Participants n=4 Participants	108 Participants n=27 Participants
Sex: Female, Male Male	25 Participants n=93 Participants	39 Participants n=4 Participants	64 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	5 Participants n=4 Participants	7 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	62 Participants n=93 Participants	72 Participants n=4 Participants	134 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=93 Participants	13 Participants n=4 Participants	31 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	9 Participants n=93 Participants	8 Participants n=4 Participants	17 Participants n=27 Participants
Race (NIH/OMB) White	64 Participants n=93 Participants	68 Participants n=4 Participants	132 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	4 Participants n=4 Participants	8 Participants n=27 Participants
Education, years	16.0 years STANDARD_DEVIATION 2.8 • n=93 Participants	16.4 years STANDARD_DEVIATION 2.4 • n=4 Participants	16.2 years STANDARD_DEVIATION 2.6 • n=27 Participants
Elixhauser comorbidity score	2.8 units on a scale STANDARD_DEVIATION 1.9 • n=93 Participants	2.3 units on a scale STANDARD_DEVIATION 1.7 • n=4 Participants	2.5 units on a scale STANDARD_DEVIATION 1.8 • n=27 Participants
Number of Risk Factors	2.5 Risk Factors STANDARD_DEVIATION 0.7 • n=93 Participants	2.4 Risk Factors STANDARD_DEVIATION 0.6 • n=4 Participants	2.5 Risk Factors STANDARD_DEVIATION 0.7 • n=27 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	SMARRT Intervention n=82 Participants 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.	Health Education Control n=90 Participants 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).
Cognitive Change	0.34 z-score Interval 0.25 to 0.42	0.19 z-score Interval 0.11 to 0.26

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	SMARRT Intervention n=82 Participants 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.	Health Education Control n=90 Participants 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).
Change in Targeted Risk Factors	0.06 z-score Interval -0.01 to 0.13	-0.05 z-score Interval -0.12 to 0.02

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	SMARRT Intervention n=82 Participants 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.	Health Education Control n=90 Participants 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).
Quality of Life Measure	12.69 score on a scale Interval 9.44 to 15.93	11.58 score on a scale Interval 8.36 to 14.79

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	SMARRT Intervention n=82 Participants 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.	Health Education Control n=90 Participants 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).
Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia	5 Participants	8 Participants

Adverse Events

SMARRT Intervention

Serious events: 24 serious events

Other events: 14 other events

Deaths: 3 deaths

Health Education Control

Serious events: 23 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	SMARRT Intervention n=82 participants at risk 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.	Health Education Control n=90 participants at risk 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).
Musculoskeletal and connective tissue disorders Non-Serious, Possibly Related	11.0% 9/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Psychiatric disorders Non-Serious, Possibly Related	2.4% 2/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Cardiac disorders Non-Serious, Possibly Related	2.4% 2/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Skin and subcutaneous tissue disorders Non-serious, Possibly Related	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.

Additional Information

Dr. Kristine Yaffe

The University of California, San Francisco

Phone: (415) 476-7307

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	SMARRT Intervention n=82 participants at risk 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.	Health Education Control n=90 participants at risk 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).
Blood and lymphatic system disorders Hospitalizations	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Cardiac disorders Hospitalizations	6.1% 5/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	4.4% 4/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Gastrointestinal disorders Hospitalizations	6.1% 5/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	4.4% 4/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
General disorders Hospitalizations	2.4% 2/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Hepatobiliary disorders Hospitalizations	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Musculoskeletal and connective tissue disorders Hospitalizations	3.7% 3/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	2.2% 2/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Renal and urinary disorders Hospitalizations	2.4% 2/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	1.1% 1/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Reproductive system and breast disorders Hospitalizations	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Respiratory, thoracic and mediastinal disorders Hospitalizations	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	1.1% 1/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Surgical and medical procedures Hospitalizations	2.4% 2/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	0.00% 0/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Life-Threatening Event	1.2% 1/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	1.1% 1/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Endocrine disorders Hospitalizations	0.00% 0/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	1.1% 1/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Infections and infestations Hospitalizations	0.00% 0/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	3.3% 3/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Vascular disorders Hospitalizations	0.00% 0/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	5.6% 5/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.
Cardiac disorders Life-Threatening Event	0.00% 0/82 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.	1.1% 1/90 • 24 months 1. Main Ascertainment: All participants are asked to report hospitalizations, new serious medical conditions, and new serious disabilities every three months, via AE form. This constitutes systematic assessment. 2. Additional Reporting: Participants randomized to the intervention arm report incidental AEs during their coaching visits and phone calls. This constitutes non-systematic assessment. All possibly related, non-serious AEs are listed. None of the SAEs are study related.