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Alzheimer DiseasePOINTERNCT03688126

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

A study testing Self-Guided Lifestyle Intervention and Structured Lifestyle Intervention in people with Alzheimer Disease, run by Wake Forest University Health Sciences at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 60 to 79 yearsHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease
What is being tested?
Self-Guided Lifestyle Intervention and Structured Lifestyle Intervention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,000 participants
Where
6 sitesUnited States
Study dates
8 Jan 2019to 16 May 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 79 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Chicagoland--Rush

    Chicago, Illinois, 60304

  • Chicagoland--Advocate Aurora Health

    Downers Grove, Illinois, 60068

  • Houston

    Houston, Texas, 77030

  • New England--Rhode Island

    Providence, Rhode Island, 02906

  • Northern California

    Sacramento, California, 95616

  • North Carolina

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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.

Read the 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.

Being tested
Self-Guided Lifestyle Intervention, Structured Lifestyle Intervention
Keywords
cognitive decline, dementia, cognitive function
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Self-Guided Lifestyle InterventionBehavioural

    Also called Self-Guided

    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 InterventionBehavioural

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

Study groups in NCT03688126
Study groupRoleWhat they receive
Self-Guided Lifestyle InterventionExperimentalLifestyle modification program that is developed by the participant to meet his/her specific needs.
Receives: Behavioral: Self-Guided Lifestyle Intervention
Structured Lifestyle InterventionExperimentalLifestyle modification program that involves participants completing structured activities that target diet, physical exercise, and intellectual and social stimulation.
Receives: Behavioral: Structured Lifestyle Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 2 years

Secondary outcomes (9)

  1. Episodic memory composite score

    This will be a composite score from PmNTB subtests Free and Cued Selective Reminding Test, Story Recall, Visual Paired Associates; and experimental measures: Cogstate One-Card Learning, Face Name Associative Memory Exam, and Behavioral Pattern Separation of Objects, calculated in a manner parallel to how the primary composite outcome is calculated. This secondary outcome is the slope of these composite scores over time (standard deviation units per year) with less negative (or positive) slopes reflecting better performance.

    Measured: up to 2 years

  2. Executive function composite score

    This will be a composite score from PmNTB subtests Number Span, Word Fluency, Trail-Making Test Part B, Digit Symbol Substitution Test; and experimental measures: Cogstate One Back, and Digital Clock Drawing Test, calculated in a manner parallel to the primary composite outcome is calculated. This secondary outcome is the slope of these composite scores over time (standard deviation units per year) with less negative (or positive) slopes reflecting better performance.

    Measured: up to 2 years

  3. Processing speed composite score

    This will be a composite score from PmNTB subtests Trail-Making Test Part A and Digit Symbol Substitution Test; and experimental measures: Cogstate Detection and Identification, and Digital Clock Drawing Test calculated in a manner parallel to the primary composite outcome is calculated. This secondary outcome is the slope of these composite scores over time (standard deviation units per year) with less negative (or positive) slopes reflecting better performance.

    Measured: up to 2 years

  4. Clinical dementia rating-sum of boxes

    The Clinical Dementia Rating (CDR) is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively) across six domains. Scores from these domains are summed ranging from 0 to 18, with higher scores reflecting worse performance. The secondary outcome will be the change in the mean scores from baseline to 2 years.

    Measured: up to 2 years

  5. Instrumental activities of daily living (IADL) score

    The Lawton-Brody IADL is a commonly used scale in clinical practice and research that assess a person's functional ability to complete tasks such as shopping, food preparation, transportation, and managing finances. Scores range from 0 to 8 for women and from 0 to 5 for men, with higher scores reflecting better performance. The secondary outcome will be the change in the mean scores from baseline to 2 years.

    Measured: up to 2 years

  6. Everyday cognition (ECog) score

    The ECog is a validated scale developed to assess everyday functional status. The short form of the instrument will be used in U.S. POINTER. Scores range from 0 to 4 with higher scores reflecting greater poorer function. The secondary outcome will be the change in the mean scores from baseline to 2 years.

    Measured: up to 2 years

  7. Digital clock drawing test (DCTClock) time

    DCTClock assesses cognition via novel software that processes information from a commercially available digital pen. This software is able to capture nuances in cognitive performance. Many metrics can be generated with this device. The secondary outcome for U.S. POINTER will be time (in seconds) to completion of the clock drawing test, with longer times reflecting poorer processing speed. The secondary outcome will be the change in the mean scores from baseline to 2 years.

    Measured: up to 2 years

  8. Lifestyle composite score

    This composite score is based on self-reported Physical Activity Questionnaire, Rush Food Frequency Questionnaire, and the Cognitive Activity Questionnaire. Participants will be ordered with respect to each index, with higher scores reflecting 1) greater daily physical activity, 2) greater conformance with the MIND Diet, and 3) greater cognitive activity. Based on these orderings, participants will be assigned percentiles with respect to each measure relative to the overall group. These percentiles will range from 0 to 100. The secondary outcome will be the average of the three percentiles. The secondary outcome will be the change in the mean scores from baseline to 2 years.

    Measured: up to 2 years

  9. Deficit accumulation frailty index score

    The Deficit Accumulation Frailty Index (DAFI) is a quantitative measure of frailty that assesses the accumulation of health deficits across various domains, including physical, cognitive, and social functions. The DAFI is calculated by dividing the number of health deficits present by the total number of possible deficits assessed. A score of 0.15 or less is typically considered non-frail, while a score of 0.25 or higher is considered frail. Scores between 0.15 and 0.25 may indicate pre-frailty.

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2018
  2. Study start8 Jan 2019
  3. Primary completion16 May 2025
  4. Study completion16 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
2,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03688126
Sponsor's protocol ID
IRB00052881
Acronym
POINTER
Status last verified
Jan 2025
First submitted
26 Sep 2018
Last updated
3 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: The data will be released to national databases upon completion of the study. Links to these databases will be provided at a later time.

Publications

  • 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.

    PubMed 25771249

  • Tangney CC, Howard M, Ventrelle J, Agarwal P, R Garcia K, Graef SM, Holland T, Jackson M, Katula J, Masdeu J, Baszlie T, Miller K, Trevino-Whitaker RA, Snyder HM, Baker LD, Espeland MA; U.S. POINTER study. Adequacy of nutrients important for brain health and dietary supplement use among older adults in the U.S. POINTER trial. J Nutr Health Aging. 2026 Nov 4;31(1):101026. doi: 10.1016/j.jnha.2026.101026. Online ahead of print.

    PubMed 42981855

  • Desai P, Howard M, Tangney CC, Stone KL, Redline S, Holland TM, Halloway S, Koncilja K, Santana JA, Whitmer RA, Espeland MA, Hayden KM, Baker LD. Napping, sleep apnea, and cognitive function: cross-sectional results from the U.S. POINTER-zzz sleep ancillary study. J Gerontol A Biol Sci Med Sci. 2026 Sep 5;81(10):glag198. doi: 10.1093/gerona/glag198.

    PubMed 42596580

  • Maillard P, Vemuri P, Harvey DJ, Harrison TM, Reddy AL, Oh H, Salloway S, Mahinrad S, Holland TM, Whitmer R, Espeland MA, Baker LD, Landau SM, DeCarli C. Age, Multidomain Lifestyle Intervention, and White Matter Integrity: Secondary Analysis of the POINTER Randomized Clinical Trial. JAMA Netw Open. 2026 Jul 1;9(7):e2620353. doi: 10.1001/jamanetworkopen.2026.20353.

    PubMed 42438415

  • Harrison TM, Harvey DJ, Chadwick T, Chao Y, Taggett J, Maillard P, Lovato L, Farias ST, Papp KV, Lockhart SN, Toga AW, Koeppe RA, Jung Y, Jagust WJ, Whitmer RA, Snyder HM, Carrillo MC, Baker LD, Espeland MA, Vemuri P, DeCarli C, Landau SM. Brain Imaging Biomarkers and Cognitive Outcomes in a Multidomain Lifestyle Intervention: The POINTER Imaging Ancillary Study. JAMA Neurol. 2026 Jun 1;83(6):521-529. doi: 10.1001/jamaneurol.2026.0832.

    PubMed 42008251

  • Espeland MA, Olson K, Tangney CC, Gitelman DR, Cleveland M, Thro AA, Demesie YN, Snyder HM, Whitmer RA, Desai P, Alam R, Crivelli L, Holland TM, Preissle O, Raman R, York MK, Baker LD; U.S. POINTER Study Group. Relative impact of multidomain lifestyle interventions on deficit accumulation frailty over 24 months in the U.S. POINTER trial. J Gerontol A Biol Sci Med Sci. 2026 Apr 7;81(5):glag094. doi: 10.1093/gerona/glag094.

    PubMed 41950390

  • 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.

    PubMed 40720610

  • 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.

    PubMed 40667673

  • 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.

    PubMed 40572055

  • 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.

    PubMed 39549282

  • 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.

    PubMed 37776210

Questions about this trial

What is this clinical trial studying?

A study testing Self-Guided Lifestyle Intervention and Structured Lifestyle Intervention in people with Alzheimer Disease, run by Wake Forest University Health Sciences at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Global cognitive function composite score (time frame: up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03688126, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2025.

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