– Two-year lifestyle intervention “recipe” tested in three NIH-funded ancillary studies –
Key Takeaways
- Findings from three NIA-funded ancillary studies to the U.S. POINTER trial described beneficial effects as measured by brain imaging, sleep health, and blood pressure regulation.
- The U.S. POINTER recipe, a 2-year multicomponent healthy lifestyle intervention with regular structured support, improved blood pressure regulation of blood flow to the brain, reduced sleep apnea respiratory events, and increased cognitive resilience for adults with certain Alzheimer’s-related brain changes.
SAN DIEGO, Dec. 2, 2025 /PRNewswire/ — A two-year multicomponent healthy lifestyle intervention with regular, structured support — which has already shown that it can improve cognition in adults at risk for cognitive decline — may also improve blood pressure regulation and reduce hourly sleep apnea respiratory events, according to new data reported today at CTAD 2025 in San Diego. The intervention may also protect against the negative cognitive effects of certain Alzheimer’s disease-related brain changes.
The healthy lifestyle recipe was created for the Alzheimer’s Association’s U.S. POINTER trial, which published its initial results in JAMA last July and reported them at AAIC 2025. The evidence-based multicomponent lifestyle intervention adapted for the U.S. population consists of regular physical exercise, the MIND diet, cognitive challenge through computerized training and other intellectual and social activities, and regular review of health metrics and goal-setting with a study clinician.
“These studies tell us that the U.S. POINTER lifestyle intervention with structured support has substantial and significant health benefits beyond improving cognition — and the benefits are in areas known to lower risk of cognitive decline and dementia,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer and medical affairs lead. “This positive relationship may multiply the beneficial impact of closely adhering to the structured U.S. POINTER ‘recipe.'”
“Bottom line, we now have a more comprehensive picture of how the U.S. POINTER intervention affects brain health, and overall health, too,” Dr. Carrillo added.
There were two versions of the intervention — structured and self-guided — that differed in intensity, structure, accountability and support provided. Trial participants in the structured intervention showed greater improvement on global cognition compared to the self-guided intervention, a benefit that likely reflects slowing of cognitive aging by one to two years.
Poor regulation of blood flow to the brain and sleep problems/irregular sleep patterns are known risk factors for cognitive decline and dementia, including Alzheimer’s disease, so these new results describe additional benefits of the U.S. POINTER structured intervention.
The new data reports came from a series of U.S. POINTER ancillary studies funded by the NIH’s National Institute on Aging (NIA):
- The U.S. POINTER Sleep Ancillary Study: POINTER-zzz
- The U.S. POINTER Neurovascular Ancillary Study: POINTER-NV
- The U.S. POINTER Neuroimaging Ancillary Study: POINTER-Neuroimaging
A fourth ancillary study, The POINTER-Microbiome Study, which presented a poster at CTAD 2025, will report more fully at a later date.
NIA Director, Dr. Richard Hodes said, “I am very encouraged by these early findings from the U.S. POINTER ancillary studies, which offer valuable insights into the physiological mechanisms that may have contributed to the positive results of the U.S. POINTER trial. The forthcoming publications and continued analysis of this rich dataset will deepen our understanding of how multimodal interventions can support brain health.”
“These studies provide an unprecedented opportunity to better understand the impact that healthy lifestyle changes can have on overall health and risk for cognitive decline and dementia,” said Dr. Kristina McLinden, Program Officer at NIA.
POINTER-zzz
In older adults, sleep disorders are highly prevalent, frequently undetected or untreated, and associated with poor brain health outcomes, including cognitive decline. This highlights sleep as a modifiable risk factor for Alzheimer’s and other diseases that cause dementia. Interventions that improve sleep may also improve cognitive function in older adults. Two components of the U.S. POINTER’s structured intervention are physical activity and healthy diet, both of which have been shown to improve overall sleep health.
The POINTER-zzz study examined whether the lifestyle changes might improve sleep quality in a subset of 780 adults who participated in the U.S. POINTER clinical trial. Nearly 65% of the study group had at least mild sleep apnea when they started the study. POINTER-zzz used simple sleep tests that were completed at home. The tests involve wearing watch-like devices overnight to measure sleep apnea, restlessness and other sleep disruptions.
Respiratory disturbances from sleep apnea declined by 1 to 2 events per hour of sleep for study participants in the structured intervention versus those in the self-guided group.
“We are excited about this finding, as it shows that the structured intervention improves not only cognition but also other behaviors that affect brain health, which may increase protection against dementia,” said Laura D. Baker, Ph.D., Professor, Internal Medicine and Public Health Sciences; and Associate Director, Wake Forest Alzheimer’s Disease Research Center at the Wake Forest University School of Medicine, Winston Salem, NC. “The positive effect of the structured intervention on sleep deepens the significance of the U.S. POINTER trial results for older Americans.” Dr. Baker is one of the Principal Investigators of the parent trial and Principal Investigator of the sleep ancillary study.
POINTER-NV
Adequate blood flow to the brain is necessary to maintain a constant supply of oxygen and nutrients. While the relevance of reduced blood flow to the brain in Alzheimer’s disease and related dementias is well documented, few studies have investigated how vascular health is essential for regulation of blood flow in the brain; this was the primary focus of the neurovascular ancillary study.
POINTER-NV enrolled 491 parent trial participants who completed comprehensive testing of vascular health at baseline, month 12, and month 24. Several types of procedures, such as ultrasound and continuous blood pressure monitoring, were used to measure the structure and function of the blood vessels in the body and in the brain.
Many POINTER-NV participants have issues that strain the heart and blood vessels, like clogged arteries, stiff arteries, or drops in blood pressure when they stand up. The researchers found significant benefits from the structured intervention on the cardiovascular system and its ability to respond to sudden changes in blood pressure, indicating improved blood pressure regulation, compared to the self-guided group. The structured intervention also improved several measures of blood-vessel health in the body’s largest artery and the main arteries supplying the brain.
“Our findings indicate that a structured multidomain lifestyle intervention can improve the body’s ability to regulate blood pressure, which is crucial for proper brain blood flow to the brain. Improved blood pressure regulation can also reduce aging-related vascular changes that allow harmful, pulsing flow of blood — too fast and too much— into the brain. These benefits may help to support cognitive function and overall brain health in U.S. POINTER participants,” said ancillary study Principal Investigators, Drs. Brinkley and Shaltout.
POINTER-Neuroimaging
POINTER-Neuroimaging is the first large-scale investigation of how lifestyle interventions affect biological markers of Alzheimer’s and dementia in the brain. Trial participants from all five main study sites were invited to receive MRI and Aβ and tau positron emission tomography (PET) imaging to assess the effects of the U.S. POINTER intervention on brain health, including (1) brain imaging biomarkers of Alzheimer’s and cerebrovascular disease and (2) cognitive benefits that were influenced by these biomarkers.
POINTER-Neuroimaging enrolled roughly 50% of the parent trial participants. The researchers found that people in the study with certain Alzheimer’s-related brain changes — lower hippocampal volume or higher tau protein build up — had greater cognitive benefits from the structured lifestyle intervention than those with these brain changes in the self-guided group. However, the presence, absence or level of amyloid in the brain did not impact the amount of cognitive benefit.
“Participating in the U.S. POINTER study’s structured intervention protected against the negative effects of tau tangle build up or smaller baseline hippocampal volume,” said Dr. Susan Landau, Principal Investigator of the ancillary study. “In other words, people with certain at-risk brain characteristics saw greater cognitive benefits following the intervention, but amyloid build up — the primary biomarker that defines Alzheimer’s disease — was not one of those at-risk characteristics. This means that people with amyloid build up experience the same benefits from the intervention as those without amyloid.”
The US POINTER ancillary studies are supported by the following NIH grants:
- POINTER-zzz: R01AG064440
- POINTER-NV: R01AG066910
- POINTER-Neuroimaging: R01AG062689
- POINTER-Microbiome: U19AG063744
About the Alzheimer’s Association®
The Alzheimer’s Association is a worldwide voluntary health organization dedicated to Alzheimer’s care, support and research. Our mission is to lead the way to end Alzheimer’s and all other dementia — by accelerating global research, driving risk reduction and early detection, and maximizing quality care and support. Our vision is a world without Alzheimer’s and all other dementia®. Visit alz.org or call +1 800.272.3900.
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