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

NCT03688126 | Completed

• 1 other identifier: IRB00052881
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 6

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.

Conditions

Alzheimer Disease

Keywords

cognitive decline; dementia; cognitive function

Outcome Measures

Primary Outcomes (1)

• Global cognitive function composite score

  Global cognitive function will be obtained from a composite score derived from subtest scores on the POINTER modified Neuropsychological Test Battery (PmNTB) that includes: Free and Cued Selective Reminding Test, Story Recall, Visual Paired Associates, Number Span, Word Fluency, Trail-Making Test, and Digit Symbol Substitution Test. Scores from each individual test will be converted to z-scores that typically range from -3 to 3, with higher scores reflecting better performance, and averaged to form a composite. The primary outcome is the slope of these composite scores over repeated assessments (standard deviation units per year), with less negative (or positive) slopes reflecting better performance.

  up to 2 years

Secondary Outcomes (9)

• Episodic memory composite score

  up to 2 years

• Executive function composite score

  up to 2 years

• Processing speed composite score

  up to 2 years

• Clinical dementia rating-sum of boxes

  up to 2 years

• Instrumental activities of daily living (IADL) score

  up to 2 years

Study Arms (2)

Self-Guided Lifestyle Intervention

EXPERIMENTAL

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

Behavioral: Self-Guided Lifestyle Intervention

Structured Lifestyle Intervention

EXPERIMENTAL

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

Behavioral: Structured Lifestyle Intervention

Interventions

Self-Guided Lifestyle Intervention BEHAVIORAL

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

Also known as: Self-Guided

Self-Guided Lifestyle Intervention

Structured Lifestyle Intervention BEHAVIORAL

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

Structured Lifestyle Intervention

Eligibility Criteria

• Age: 60 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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)
• 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)

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Alzheimer's Association: collaborator

Study Sites (6)

Northern California

Sacramento, California, 95616, United States

Location

Chicagoland--Rush

Chicago, Illinois, 60304, United States

Location

Chicagoland--Advocate Aurora Health

Downers Grove, Illinois, 60068, United States

Location

North Carolina

Winston-Salem, North Carolina, 27157, United States

Location

New England--Rhode Island

Providence, Rhode Island, 02906, United States

Location

Houston

Houston, Texas, 77030, United States

Location

Related Publications (6)

• 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.

  PMID: 25771249 BACKGROUND

• 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.

  PMID: 40720610 DERIVED

• 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.

  PMID: 40667673 DERIVED

• 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.

  PMID: 40572055 DERIVED

• 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.

  PMID: 39549282 DERIVED

• 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.

  PMID: 37776210 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Laura D Baker, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Mark A Espeland, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Rachel A Whitmer, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Miia Kivipelto, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The U.S. POINTER Coordinating Center (CC) is divided into two distinct entities: the Administrative and Clinical Operations CC and the Data CC. Investigators and staff within the Administrative and Clinical Operations CC will be masked to outcomes data. Investigators and staff within the Data CC will be unmasked to intervention assignment and outcomes. In the clinic, examiners, data entry staff, and the study clinician will be masked to intervention assignment.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 28, 2018
• Study Start: January 8, 2019
• Primary Completion: May 16, 2025
• Study Completion: May 16, 2025
• Last Updated: November 3, 2025

Record last verified: 2025-01

Locations

US (6)