U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk

NCT ID: NCT03688126

Last Updated: 2025-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-08
• Study Completion Date: 2025-05-16

Brief Summary

The purpose of this research study is to see if lifestyle changes can protect memory and thinking (cognition) as we age. A recent study in Finland found that a combination of physical and cognitive exercise, diet, and social activity protected cognitive function in healthy older adults who were at increased risk of significant memory loss. So far no medications can rival this positive outcome. The point of POINTER is to test if lifestyle change can also protect against memory loss in Americans.

Detailed Description

Lifestyle interventions focused on combining healthy diet, physical activity, and social and intellectual challenges may represent a promising therapeutic strategy to protect brain health. The recent results of the population-based 2-year clinical trial, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), indicated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities, and management of heart health risk factors protected cognitive function in healthy older adults at increased risk of cognitive decline. As yet, there are no pharmacological treatment options that can rival this effect. Thus, there is an urgent need to expand this work to test the generalizability, adaptability and sustainability of its findings in diverse and global populations. This pivotal U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) will test whether a similar 2-year intensive lifestyle intervention, adapted to American culture and delivered within the community, can protect cognitive function in older adults in the U.S. who are at increased risk for cognitive decline and dementia. If successful, the results of this study will have large-scale implications for public policy regarding standard of clinical care and prescriptive practices for a fast-growing and vulnerable population of older adults.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Self-Guided Lifestyle Intervention

Lifestyle modification program that is developed by the participant to meet his/her specific needs.

Group Type: EXPERIMENTAL

Self-Guided Lifestyle Intervention

Intervention Type: BEHAVIORAL

Lifestyle intervention that involves providing participants with education, support, and tangible tools to assist them in developing and carrying out healthier lifestyle practices.

Structured Lifestyle Intervention

Lifestyle modification program that involves participants completing structured activities that target diet, physical exercise, and intellectual and social stimulation.

Group Type: EXPERIMENTAL

Structured Lifestyle Intervention

Intervention Type: BEHAVIORAL

Lifestyle intervention that involves a structured program of diet, physical and cognitive exercise, and management of cardiometabolic risks.

Interventions

Self-Guided Lifestyle Intervention

Lifestyle intervention that involves providing participants with education, support, and tangible tools to assist them in developing and carrying out healthier lifestyle practices.

Intervention Type: BEHAVIORAL

Structured Lifestyle Intervention

Lifestyle intervention that involves a structured program of diet, physical and cognitive exercise, and management of cardiometabolic risks.

Intervention Type: BEHAVIORAL

Other Intervention Names

Self-Guided

Eligibility Criteria

Inclusion Criteria

• Sedentary (not a regular exerciser, determined using the POINTER--modified Telephone Assessment of Physical Activity [TAPA]
• Low MIND Diet score (determined using the MIND Diet Screener)
• No cognitive impairment as per Telephone Interview for Cognitive Status (mTICS) score >32 (includes adjustments for demographics such as age, education and race), the Clinical Dementia Rating Scale (CDR <0.5), and the CDR-Sum of Boxes (CDR-SB <1)
• Risk Score for cognitive decline >2, using the following scoring algorithm:1 point: Suboptimum cardiovascular health (treated or untreated): systolic Blood Pressure >125 mmHg ~OR~ low-density lipoprotein (LDL) cholesterol >115 mg/dL~OR~ glycated hemoglobin (HbA1c) >6.0%1 point: First degree family history (mother, father, sister, brother) of memory impairment- 1 point: Race and ethnicity: African American/Black, Native American, Middle Eastern/North African, or Hispanic/Latinx

1 point: Older age: 70-79 years 1 point: Sex: male

• Lives in a region where the POINTER interventions will be delivered
• Does not plan to travel outside of the home geographic area for an extended period of time during study participation
• Capacity to complete physical exercise
• Willing to complete all study-related activities for at least 24 months
• Willing to be randomized to either lifestyle intervention group

Exclusion Criteria

• Age <60 or ≥80 years
• Any significant neurologic disease, including any form of dementia, mild cognitive impairment, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
• History of major depression within the last 6 months
• History of bipolar disorder or schizophrenia as per Diagnostic and Statistical Manual (DSM) V criteria
• History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria
• Current or past use of medications for memory impairment or AD (e.g., cholinesterase inhibitors, memantine)
• Current daily use of systemic corticosteroids
• Current use of 3 or more doses of narcotics/week. Use of intermittent narcotics should be stopped 48 hours prior to clinic visits/cognitive testing. Tramadol is allowed as long as the dose remains stable for 3 months.
• Use of psychoactive medications, including benzodiazepines, tricyclic antidepressants, antipsychotics, mood-stabilizers, psychostimulants, anti- parkinsonian medications, anticonvulsant medications or medications with significant central anticholinergic activity are allowed as long as the medication is NOT used to treat an exclusionary medical condition.
• Significant cardiovascular disease (including New York Heart Association (NYHA) Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest, or uncontrolled angina)
• Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled arrhythmia, or new Q waves or ST-segment depressions (>3 mm) on ECG (treated atrial fibrillation for more than 1 year or occasional premature ventricular contractions on ECG are not exclusions)
• Myocardial infarction, major heart surgery (i.e., valve replacement, bypass surgery, stent placement, angioplasty), deep vein thrombosis, or pulmonary embolus in the past 6 months
• Large vessel stroke in the past 2 years
• History of transient ischemic attack (TIA) or small vessel stroke in the last 6 months; TIA occurring more than 6 months ago with residual effects
• Current use of insulin to treat type 2 diabetes
• Lung disease requiring either regular use of corticosteroids or the use of supplemental oxygen; intermittent use of corticosteroids or supplemental oxygen to treat chronic obstructive pulmonary disease exacerbation is allowed; use of inhaled steroids for asthma is allowed
• End stage renal disease (e.g., requiring dialysis or as per clinician discretion)
• Clinically significant abnormalities in laboratory blood tests as per judgment of the site Study Clinician
• History within the last 2 years of treatment for primary or recurrent malignant disease, excluding non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post treatment; long-term endocrine therapy for breast cancer is allowed (e.g., tamoxifen, anastrozole)
• History of hip fracture, joint replacement, or spinal surgery in the last 6 months
• Currently receiving physical therapy or cardiopulmonary rehabilitation
• History of a malabsorptive bariatric procedure (gastric bypass, biliopancreatic diversion); other bariatric procedures involving restriction (i.e., sleeve, band) are not exclusionary
• Resides in an assisted living facility or nursing home
• Receives hospice care
• Site PI/Study Clinician discretion regarding medical status, appropriateness of participation or concern about intervention adherence

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alzheimer's Association

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura D Baker, PhD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Mark A Espeland, PhD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Rachel A Whitmer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Miia Kivipelto, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Northern California

Sacramento, California, United States

Chicagoland--Rush

Chicago, Illinois, United States

Chicagoland--Advocate Aurora Health

Downers Grove, Illinois, United States

North Carolina

Winston-Salem, North Carolina, United States

New England--Rhode Island

Providence, Rhode Island, United States

Houston

Houston, Texas, United States

Countries

United States

References

Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.

Reference Type: BACKGROUND

PMID: 25771249 (View on PubMed)

Baker LD, Espeland MA, Whitmer RA, Snyder HM, Leng X, Lovato L, Papp KV, Yu M, Kivipelto M, Alexander AS, Antkowiak S, Cleveland M, Day C, Elbein R, Tomaszewski Farias S, Felton D, Garcia KR, Gitelman DR, Graef S, Howard M, Katula J, Lambert K, Matongo O, McDonald AM, Pavlik V, Raman R, Salloway S, Tangney C, Ventrelle J, Wilmoth S, Willliams BJ, Wing R, Woolard N, Carrillo MC. Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial. JAMA. 2025 Aug 26;334(8):681-691. doi: 10.1001/jama.2025.12923.

Reference Type: DERIVED

PMID: 40720610 (View on PubMed)

Papp KV, Farias ST, Howard M, Thro A, Ngandu T, Caudle B, Sachs BC, Chan M, Krueger KR, Hartman ERT, Lee A, York MK, Austin MT, Demos KE, Holland TM, Leng X, Raman R, Snyder HM, Carrillo MC, Whitmer RA, Espeland MA, Baker LD; US POINTER Study Group. Baseline cognition and demographic, lifestyle, and cardiovascular risk factors in US POINTER. Alzheimers Dement. 2025 Jul;21(7):e70216. doi: 10.1002/alz.70216.

Reference Type: DERIVED

PMID: 40667673 (View on PubMed)

Tomaszewski Farias S, Leng I, Papp K, Mehra A, Chan M, York M, Sachs BC, Krueger KR, Lee A, Whitmer R, Snyder HM, Baker LD; U.S. POINTER Study Group. Subjective cognitive decline among diverse older adults: Prevalence and associations with objective cognition. Alzheimers Dement. 2025 Jul;21(7):e70432. doi: 10.1002/alz.70432.

Reference Type: DERIVED

PMID: 40572055 (View on PubMed)

Baker LD, Snyder HM, Espeland MA, Whitmer RA, Kivipelto M, Woolard N, Katula J, Papp KV, Ventrelle J, Graef S, Hill MA, Rushing S, Spell J, Lovato L, Felton D, Williams BJ, Ghadimi Nouran M, Raman R, Ngandu T, Solomon A, Wilmoth S, Cleveland ML, Williamson JD, Lambert KL, Tomaszewski Farias S, Day CE, Tangney CC, Gitelman DR, Matongo O, Reynolds T, Pavlik VN, Yu MM, Alexander AS, Elbein R, McDonald AM, Salloway S, Wing RR, Antkowiak S, Morris MC, Carrillo MC; U.S. POINTER Study Group. Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER). Alzheimers Dement. 2024 Feb;20(2):769-782. doi: 10.1002/alz.13365. Epub 2023 Sep 30.

Reference Type: DERIVED

PMID: 37776210 (View on PubMed)

Espeland MA, Demesie YN, Olson K, Lockhart SN, Farias SET, Cleveland ML, Tangney CC, Crivelli L, Snyder HM, York MK, Baker LD, Whitmer RA, Wing RR, Garcia KR, Callahan KE. Associations Between Deficit Accumulation Frailty and Baseline Markers of Lifestyle in the U.S. POINTER Trial. J Gerontol A Biol Sci Med Sci. 2025 Jan 16;80(2):glae279. doi: 10.1093/gerona/glae279.

Reference Type: DERIVED

PMID: 39549282 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

IRB00052881

Identifier Type: -

Identifier Source: org_study_id