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| Name | Class |
|---|---|
| University of California, San Francisco | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SMARRT Intervention | Active Comparator | The SMARRT intervention team will use a standardized procedure to develop an individualized Alzheimer's risk profile for each participant randomized to the SMARRT intervention arm. Participants will then meet in-person with an interventionist to review their risk profile and develop an initial personalized risk reduction action plan. For the few participants enrolled during COVID, initial interventionist visits were conducted by phone. Targeted areas will include: 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. |
|
| Health Education Intervention | Active Comparator | Participants in the Health Education arm will be mailed general information that will address factors that will be 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 will not be provided with personalized information about their risk of Alzheimer's and dementia. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SMARRT Intervention | Behavioral | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 Years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sascha Dublin, MD, PhD | Kaiser Permanente | Principal Investigator |
| Kristine Yaffe, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kaiser Permanente Washington Health Research Institute | Seattle | Washington | 98101 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Alzheimer's Disease International. World Alzheimer Report 2015: The Global Impact of Dementia, An Analysis of Prevalence, Incidence, Cost and Trends. London: Alzheimer's Disease International (ADI); 2015. | ||
| 21414557 | Background | Alzheimer's Association. 2011 Alzheimer's disease facts and figures. Alzheimers Dement. 2011 Mar;7(2):208-44. doi: 10.1016/j.jalz.2011.02.004. | |
| 29318278 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | z-score | 2 Years |
24 months
None of the SAEs are study related.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalizations | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-Serious, Possibly Related | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Calf cramps, joint pain, muscle pulls |
Our trial was initiated prior to the COVID-19 pandemic, but the shutdown shortened the enrollment period and necessitated administering the intervention and measuring the outcomes remotely.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kristine Yaffe | The University of California, San Francisco | (415) 476-7307 | kristine.yaffe@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 26, 2023 | Jun 26, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003704 | Dementia |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
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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).
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| Health Education Intervention | Behavioral | 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). |
|
| 2 Years |
| 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. | 2 Years |
| 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. | 2 Years |
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| 29282327 | Background | Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens J, Rae-Grant A. Practice guideline update summary: Mild cognitive impairment [RETIRED]: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Jan 16;90(3):126-135. doi: 10.1212/WNL.0000000000004826. Epub 2017 Dec 27. |
| 21514248 | Background | Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21. |
| 15324367 | Background | Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004 Sep;256(3):240-6. doi: 10.1111/j.1365-2796.2004.01380.x. |
| Background | Cohen J. Statistical power analysis for the behavioral sciences (2nd ed). Hillsdale, N.J.: Lawrence Earlbaum Associates; 1988. |
| 17397440 | Background | Li C, Friedman B, Conwell Y, Fiscella K. Validity of the Patient Health Questionnaire 2 (PHQ-2) in identifying major depression in older people. J Am Geriatr Soc. 2007 Apr;55(4):596-602. doi: 10.1111/j.1532-5415.2007.01103.x. |
| 18752852 | Background | Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH. The PHQ-8 as a measure of current depression in the general population. J Affect Disord. 2009 Apr;114(1-3):163-73. doi: 10.1016/j.jad.2008.06.026. Epub 2008 Aug 27. |
| 38010725 | Derived | Yaffe K, Vittinghoff E, Dublin S, Peltz CB, Fleckenstein LE, Rosenberg DE, Barnes DE, Balderson BH, Larson EB. Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial. JAMA Intern Med. 2024 Jan 1;184(1):54-62. doi: 10.1001/jamainternmed.2023.6279. |
| Death |
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| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Education, years | Years of formal education completed. For example, 12 years = High School Graduate. | Mean | Standard Deviation | years |
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| Elixhauser comorbidity score | The Elixhauser Comorbidity Index (Elixhauser, 1998) is a risk score that measures the overall severity of comorbid illnesses (using diagnostic codes). Scores can range from 0 to 31. Higher scores represent higher severity of comorbid illnesses in the year prior to baseline and are associated with higher risk of mortality and hospital resource use. | Mean | Standard Deviation | units on a scale |
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| Number of Risk Factors | Average number of risk factors present at baseline, out of a total of 8 risk factors. | Mean | Standard Deviation | Risk Factors |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | z-score | 2 Years |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | 2 Years |
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| 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. | 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. | Posted | Count of Participants | Participants | 2 Years |
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| 3 |
| 82 |
| 24 |
| 82 |
| 14 |
| 82 |
| EG001 | 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). | 1 | 90 | 23 | 90 | 0 | 90 |
| Hospitalizations | Cardiac disorders | Systematic Assessment |
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| Hospitalizations | Gastrointestinal disorders | Systematic Assessment |
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| Hospitalizations | General disorders | Systematic Assessment |
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| Hospitalizations | Hepatobiliary disorders | Systematic Assessment |
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| Hospitalizations | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Hospitalizations | Renal and urinary disorders | Systematic Assessment |
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| Hospitalizations | Reproductive system and breast disorders | Systematic Assessment |
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| Hospitalizations | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hospitalizations | Surgical and medical procedures | Systematic Assessment |
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| Life-Threatening Event | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Hospitalizations | Endocrine disorders | Systematic Assessment |
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| Hospitalizations | Infections and infestations | Systematic Assessment |
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| Hospitalizations | Vascular disorders | Systematic Assessment |
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| Life-Threatening Event | Cardiac disorders | Systematic Assessment |
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| Non-Serious, Possibly Related | Psychiatric disorders | Non-systematic Assessment | Study-related anxiety |
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| Non-Serious, Possibly Related | Cardiac disorders | Non-systematic Assessment | High blood pressure at study visit |
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| Non-serious, Possibly Related | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Rash from activity monitor |
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Not provided
Not provided
| D001523 | Mental Disorders |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |